Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c
- Zhou, Bin, Sheffer, Kate, Bennett, James, Gregg, Edward, Danaei, Goodarz, Singleton, Rosie, Shaw, Jonathan, Mishra, Anu, Lhoste, Victor, Carrillo-Larco, Rodrigo, Kengne, Andre, Phelps, Nowell, Heap, Rachel, Rayner, Archie, Stevens, Gretchen, Paciorek, Chris, Riley, Leanne, Cowan, Melanie, Savin, Stefan, Vander Hoorn, Stephen, Lu, Yuan, Pavkov, Meda, Imperatore, Giuseppina, Aguilar-Salinas, Carlos, Ahmad, Noor, Anjana, Ranjit, Davletov, Kairat, Farzadfar, Farshad, González-Villalpando, Clicerio, Charchar, Fadi
- Authors: Zhou, Bin , Sheffer, Kate , Bennett, James , Gregg, Edward , Danaei, Goodarz , Singleton, Rosie , Shaw, Jonathan , Mishra, Anu , Lhoste, Victor , Carrillo-Larco, Rodrigo , Kengne, Andre , Phelps, Nowell , Heap, Rachel , Rayner, Archie , Stevens, Gretchen , Paciorek, Chris , Riley, Leanne , Cowan, Melanie , Savin, Stefan , Vander Hoorn, Stephen , Lu, Yuan , Pavkov, Meda , Imperatore, Giuseppina , Aguilar-Salinas, Carlos , Ahmad, Noor , Anjana, Ranjit , Davletov, Kairat , Farzadfar, Farshad , González-Villalpando, Clicerio , Charchar, Fadi
- Date: 2023
- Type: Text , Journal article
- Relation: Nature Medicine Vol. 29, no. 11 (2023), p. 2885-2901
- Full Text:
- Reviewed:
- Description: Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29–39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance. © 2023, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Fadi Charchar" is provided in this record**
- Authors: Zhou, Bin , Sheffer, Kate , Bennett, James , Gregg, Edward , Danaei, Goodarz , Singleton, Rosie , Shaw, Jonathan , Mishra, Anu , Lhoste, Victor , Carrillo-Larco, Rodrigo , Kengne, Andre , Phelps, Nowell , Heap, Rachel , Rayner, Archie , Stevens, Gretchen , Paciorek, Chris , Riley, Leanne , Cowan, Melanie , Savin, Stefan , Vander Hoorn, Stephen , Lu, Yuan , Pavkov, Meda , Imperatore, Giuseppina , Aguilar-Salinas, Carlos , Ahmad, Noor , Anjana, Ranjit , Davletov, Kairat , Farzadfar, Farshad , González-Villalpando, Clicerio , Charchar, Fadi
- Date: 2023
- Type: Text , Journal article
- Relation: Nature Medicine Vol. 29, no. 11 (2023), p. 2885-2901
- Full Text:
- Reviewed:
- Description: Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29–39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance. © 2023, The Author(s). **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Fadi Charchar" is provided in this record**
Adjustment for body mass index changes inverse associations of HDL-cholesterol with blood pressure and hypertension to positive associations
- Yang, Guang, Qian, Tingting, Sun, Hui, Xu, Qun, Hou, Xujuan, Hu, Wenqi, Zhang, Guang, Drummond, Grant, Sobey, Christopher, Witting, Paul, Denton, Kate, Charchar, Fadi, Golledge, Jonathan, Wang, Yutang
- Authors: Yang, Guang , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Drummond, Grant , Sobey, Christopher , Witting, Paul , Denton, Kate , Charchar, Fadi , Golledge, Jonathan , Wang, Yutang
- Date: 2022
- Type: Text , Journal article
- Relation: Journal of Human Hypertension Vol. 36, no. 6 (2022), p. 570-579
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: The associations between high-density lipoprotein cholesterol (HDL-C) and blood pressure (BP) or hypertension are inconsistent in previous studies. This study aimed to assess these associations in a large cohort of Chinese adults and across different age groups. This cross-sectional association study included 22,081 Chinese adults. Associations of HDL-C with BP and hypertension were analyzed using linear or logistic regression, with or without adjustment for confounding factors. HDL-C was inversely associated with BP and hypertension. These associations were still apparent after adjustment for age, sex, fasting plasma glucose, and low-density lipoprotein cholesterol. Sub-analyses revealed: (1) in the whole cohort and females alone, HDL-C was inversely associated with BP and hypertension in young and middle-aged but not older participants; (2) in males alone, HDL-C was not associated with systolic BP or hypertension. However, HDL-C was either inversely, or not, or positively associated with BP in young, middle-aged, and older males, respectively. After further adjustment for body mass index (BMI), the negative associations of HDL-C with BP and hypertension in the whole cohort became positive ones, and the positive associations only presented in males. These findings suggest that further adjustment for BMI changes inverse associations of HDL-cholesterol with BP and hypertension to positive associations in a cohort of Chinese adults. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
- Authors: Yang, Guang , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Drummond, Grant , Sobey, Christopher , Witting, Paul , Denton, Kate , Charchar, Fadi , Golledge, Jonathan , Wang, Yutang
- Date: 2022
- Type: Text , Journal article
- Relation: Journal of Human Hypertension Vol. 36, no. 6 (2022), p. 570-579
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: The associations between high-density lipoprotein cholesterol (HDL-C) and blood pressure (BP) or hypertension are inconsistent in previous studies. This study aimed to assess these associations in a large cohort of Chinese adults and across different age groups. This cross-sectional association study included 22,081 Chinese adults. Associations of HDL-C with BP and hypertension were analyzed using linear or logistic regression, with or without adjustment for confounding factors. HDL-C was inversely associated with BP and hypertension. These associations were still apparent after adjustment for age, sex, fasting plasma glucose, and low-density lipoprotein cholesterol. Sub-analyses revealed: (1) in the whole cohort and females alone, HDL-C was inversely associated with BP and hypertension in young and middle-aged but not older participants; (2) in males alone, HDL-C was not associated with systolic BP or hypertension. However, HDL-C was either inversely, or not, or positively associated with BP in young, middle-aged, and older males, respectively. After further adjustment for body mass index (BMI), the negative associations of HDL-C with BP and hypertension in the whole cohort became positive ones, and the positive associations only presented in males. These findings suggest that further adjustment for BMI changes inverse associations of HDL-cholesterol with BP and hypertension to positive associations in a cohort of Chinese adults. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
Molecular insights into genome-wide association studies of chronic kidney disease-defining traits
- Xu, Xiaoguang, Eales, James, Akbarov, Artur, Guo, Hui, Becker, Lorenz, Talavera, David, Ashraf, Fehzan, Nawaz, Jabran, Pramanik, Sanjeev, Bowes, John, Jiang, Xiao, Dormer, John, Denniff, Matthew, Antczak, Andrzej, Szulinska, Monika, Wise, Ingrid, Prestes, Priscilla, Glyda, Maciej, Bogdanski, Pawel, Zukowska-Szczechowska, Ewa, Berzuini, Carlo, Woolf, Adrian, Samani, Nilesh, Charchar, Fadi, Tomaszewski, Maciej
- Authors: Xu, Xiaoguang , Eales, James , Akbarov, Artur , Guo, Hui , Becker, Lorenz , Talavera, David , Ashraf, Fehzan , Nawaz, Jabran , Pramanik, Sanjeev , Bowes, John , Jiang, Xiao , Dormer, John , Denniff, Matthew , Antczak, Andrzej , Szulinska, Monika , Wise, Ingrid , Prestes, Priscilla , Glyda, Maciej , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Berzuini, Carlo , Woolf, Adrian , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2018
- Type: Text , Journal article
- Relation: Nature communications Vol. 9, no. 1 (2018), p. 1-12
- Full Text:
- Reviewed:
- Description: Genome-wide association studies (GWAS) have identified >100 loci of chronic kidney disease-defining traits (CKD-dt). Molecular mechanisms underlying these associations remain elusive. Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues we uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci. Our colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate. We identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal. These data highlight the variants and genes underpinning the associations uncovered in GWAS of CKD-dt.
- Authors: Xu, Xiaoguang , Eales, James , Akbarov, Artur , Guo, Hui , Becker, Lorenz , Talavera, David , Ashraf, Fehzan , Nawaz, Jabran , Pramanik, Sanjeev , Bowes, John , Jiang, Xiao , Dormer, John , Denniff, Matthew , Antczak, Andrzej , Szulinska, Monika , Wise, Ingrid , Prestes, Priscilla , Glyda, Maciej , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Berzuini, Carlo , Woolf, Adrian , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2018
- Type: Text , Journal article
- Relation: Nature communications Vol. 9, no. 1 (2018), p. 1-12
- Full Text:
- Reviewed:
- Description: Genome-wide association studies (GWAS) have identified >100 loci of chronic kidney disease-defining traits (CKD-dt). Molecular mechanisms underlying these associations remain elusive. Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues we uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci. Our colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate. We identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal. These data highlight the variants and genes underpinning the associations uncovered in GWAS of CKD-dt.
Contributions of obesity to kidney health and disease: insights from Mendelian randomization and the human kidney transcriptomics
- Xu, Xiaoguang, Eales, James, Jiang, Xiao, Sanderson, Eleanor, Drzal, Maciej, Saluja, Sushant, Scannali, David, Williams, Bryan, Morris, Andrew, Guzik, Tomasz, Charchar, Fadi, Holmes, Michael, Tomaszewski, Maciej
- Authors: Xu, Xiaoguang , Eales, James , Jiang, Xiao , Sanderson, Eleanor , Drzal, Maciej , Saluja, Sushant , Scannali, David , Williams, Bryan , Morris, Andrew , Guzik, Tomasz , Charchar, Fadi , Holmes, Michael , Tomaszewski, Maciej
- Date: 2022
- Type: Text , Journal article
- Relation: Cardiovascular research Vol. 118, no. 15 (2022), p. 3151-3161
- Full Text:
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- Description: AIMS: Obesity and kidney diseases are common complex disorders with an increasing clinical and economic impact on healthcare around the globe. Our objective was to examine if modifiable anthropometric obesity indices show putatively causal association with kidney health and disease and highlight biological mechanisms of potential relevance to the association between obesity and the kidney. METHODS AND RESULTS: We performed observational, one-sample, two-sample Mendelian randomization (MR) and multivariable MR studies in
- Authors: Xu, Xiaoguang , Eales, James , Jiang, Xiao , Sanderson, Eleanor , Drzal, Maciej , Saluja, Sushant , Scannali, David , Williams, Bryan , Morris, Andrew , Guzik, Tomasz , Charchar, Fadi , Holmes, Michael , Tomaszewski, Maciej
- Date: 2022
- Type: Text , Journal article
- Relation: Cardiovascular research Vol. 118, no. 15 (2022), p. 3151-3161
- Full Text:
- Reviewed:
- Description: AIMS: Obesity and kidney diseases are common complex disorders with an increasing clinical and economic impact on healthcare around the globe. Our objective was to examine if modifiable anthropometric obesity indices show putatively causal association with kidney health and disease and highlight biological mechanisms of potential relevance to the association between obesity and the kidney. METHODS AND RESULTS: We performed observational, one-sample, two-sample Mendelian randomization (MR) and multivariable MR studies in
Epigenetic modifications in essential hypertension
- Wise, Ingrid, Charchar, Fadi
- Authors: Wise, Ingrid , Charchar, Fadi
- Date: 2016
- Type: Text , Journal article , Review
- Relation: International Journal of Molecular Sciences Vol. 17, no. 4 (2016), p. 1-14
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: Essential hypertension (EH) is a complex, polygenic condition with no single causative agent. Despite advances in our understanding of the pathophysiology of EH, hypertension remains one of the world’s leading public health problems. Furthermore, there is increasing evidence that epigenetic modifications are as important as genetic predisposition in the development of EH. Indeed, a complex and interactive genetic and environmental system exists to determine an individual’s risk of EH. Epigenetics refers to all heritable changes to the regulation of gene expression as well as chromatin remodelling, without involvement of nucleotide sequence changes. Epigenetic modification is recognized as an essential process in biology, but is now being investigated for its role in the development of specific pathologic conditions, including EH. Epigenetic research will provide insights into the pathogenesis of blood pressure regulation that cannot be explained by classic Mendelian inheritance. This review concentrates on epigenetic modifications to DNA structure, including the influence of non-coding RNAs on hypertension development. © 2016 by the authors; licensee MDPI, Basel, Switzerland.
- Authors: Wise, Ingrid , Charchar, Fadi
- Date: 2016
- Type: Text , Journal article , Review
- Relation: International Journal of Molecular Sciences Vol. 17, no. 4 (2016), p. 1-14
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: Essential hypertension (EH) is a complex, polygenic condition with no single causative agent. Despite advances in our understanding of the pathophysiology of EH, hypertension remains one of the world’s leading public health problems. Furthermore, there is increasing evidence that epigenetic modifications are as important as genetic predisposition in the development of EH. Indeed, a complex and interactive genetic and environmental system exists to determine an individual’s risk of EH. Epigenetics refers to all heritable changes to the regulation of gene expression as well as chromatin remodelling, without involvement of nucleotide sequence changes. Epigenetic modification is recognized as an essential process in biology, but is now being investigated for its role in the development of specific pathologic conditions, including EH. Epigenetic research will provide insights into the pathogenesis of blood pressure regulation that cannot be explained by classic Mendelian inheritance. This review concentrates on epigenetic modifications to DNA structure, including the influence of non-coding RNAs on hypertension development. © 2016 by the authors; licensee MDPI, Basel, Switzerland.
Reduced renal function may explain the higher prevalence of hyperuricemia in older people
- Wang, Yutang, Zhang, Wanlin, Qian, Tingting, Sun, Hui, Xu, Qun, Hou, Xujuan, Hu, Wenqi, Zhang, Guang, Drummond, Grant, Sobey, Chris, Charchar, Fadi, Golledge, Jonathan, Yang, Guang
- Authors: Wang, Yutang , Zhang, Wanlin , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Drummond, Grant , Sobey, Chris , Charchar, Fadi , Golledge, Jonathan , Yang, Guang
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: This study aimed to investigate the contribution of renal dysfunction to enhanced hyperuricemia prevalence in older people. A cohort of 13,288 Chinese people aged between 40 and 95 years were recruited from January to May 2019. Serum uric acid concentration and estimated glomerular filtration rate [eGFR] were measured. The associations between age or eGFR and serum uric acid or hyperuricemia were analyzed using linear or binary logistic regression adjusting for risk factors. Uric acid concentration and prevalence of hyperuricemia were greater in older participants. Adjustment for reduced renal function (eGFR < 60 mL/min/1.73 m2) eliminated the associations between older age and higher uric acid concentration and between older age and higher prevalence of hyperuricemia diagnosis, whereas adjustment for other risk factors did not change those associations. Lower eGFR was associated with higher uric acid concentration both before (β = − 0.296, P < 0.001) and after adjustment for age (β = − 0.313, P < 0.001). Reduced renal function was associated with hyperuricemia diagnosis both before (odds ratio, OR, 3.64; 95% CI 3.10–4.28; P < 0.001) and after adjustment for age (adjusted OR, 3.82; 95% CI 3.22–4.54; P < 0.001). Mean serum uric acid and prevalence of hyperuricemia were higher in people with eGFR < 60 mL/min/1.73 m2 than those with eGFR ≥ 60 mL/min/1.73 m2. The prevalence of reduced renal function increased with older age (P < 0.001). This study suggests that reduced renal function can explain the increased uric acid levels and hyperuricemia diagnoses in older people. © 2021, The Author(s).
- Authors: Wang, Yutang , Zhang, Wanlin , Qian, Tingting , Sun, Hui , Xu, Qun , Hou, Xujuan , Hu, Wenqi , Zhang, Guang , Drummond, Grant , Sobey, Chris , Charchar, Fadi , Golledge, Jonathan , Yang, Guang
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: This study aimed to investigate the contribution of renal dysfunction to enhanced hyperuricemia prevalence in older people. A cohort of 13,288 Chinese people aged between 40 and 95 years were recruited from January to May 2019. Serum uric acid concentration and estimated glomerular filtration rate [eGFR] were measured. The associations between age or eGFR and serum uric acid or hyperuricemia were analyzed using linear or binary logistic regression adjusting for risk factors. Uric acid concentration and prevalence of hyperuricemia were greater in older participants. Adjustment for reduced renal function (eGFR < 60 mL/min/1.73 m2) eliminated the associations between older age and higher uric acid concentration and between older age and higher prevalence of hyperuricemia diagnosis, whereas adjustment for other risk factors did not change those associations. Lower eGFR was associated with higher uric acid concentration both before (β = − 0.296, P < 0.001) and after adjustment for age (β = − 0.313, P < 0.001). Reduced renal function was associated with hyperuricemia diagnosis both before (odds ratio, OR, 3.64; 95% CI 3.10–4.28; P < 0.001) and after adjustment for age (adjusted OR, 3.82; 95% CI 3.22–4.54; P < 0.001). Mean serum uric acid and prevalence of hyperuricemia were higher in people with eGFR < 60 mL/min/1.73 m2 than those with eGFR ≥ 60 mL/min/1.73 m2. The prevalence of reduced renal function increased with older age (P < 0.001). This study suggests that reduced renal function can explain the increased uric acid levels and hyperuricemia diagnoses in older people. © 2021, The Author(s).
A modified MTS proliferation assay for suspended cells to avoid the interference by hydralazine and β-Mercaptoethanol
- Wang, Yutang, Nguyen, Dinh, Anesi, Jack, Kelly, Jason, Ahmady, Fahima, Charchar, Fadi
- Authors: Wang, Yutang , Nguyen, Dinh , Anesi, Jack , Kelly, Jason , Ahmady, Fahima , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Assay and Drug Development Technologies Vol. 19, no. 3 (2021), p. 184-190. https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay is one of the most commonly used tests of cell proliferation. Hydralazine has been reported to interfere with the performance of the MTS assay when used on adherent cells. This study aimed to investigate whether hydralazine interferes with the performance of the MTS assay on suspended cells. THP-1 (a monocytic leukemia cell line) cells were cultured in the presence or absence of hydralazine (0, 10, 50, 100, and 500 μM) for 2 or 24 h. Cell numbers were analyzed using the MTS, trypan blue exclusion, or microscopic assays. A modified version of the standard MTS assay was established by centrifuging the cells and replacing the test medium with fresh culture medium immediately before the addition of the MTS reagent. Culture of THP-1 cells with hydralazine at concentrations of 50, 100, and 500 μM for 2 h increased absorbance (p < 0.001) in the standard MTS assay, whereas both the trypan blue exclusion assay and microscopy suggested no change in cell numbers. Culture of THP-1 cells with 100 and 500 μm hydralazine for 24 h increased absorbance (p < 0.05) in the standard MTS assay; however, trypan blue exclusion and microscopy suggested a decrease in cell numbers. In a cell-free system, hydralazine (100 and 500 μM) increased absorbance in a time- and concentration-dependent manner. The modified MTS assay produced results consistent with trypan blue exclusion and microscopy using THP-1 cells. In addition, the modified MTS assay produced reliable results when K562 and Jurkat cells were incubated with hydralazine or β-mercaptoethanol (βME). In conclusion, a simple modification of the standard MTS assay overcame the interference of hydralazine and βME when assessing suspended cells. © Copyright 2021, Mary Ann Liebert, Inc., publishers 2021. *Please note that there are multiple authors for this article therefore only the name of the Federation University Australia affiliates “Yutang Wang, Dinh Nguyen, Jack Anesi, Jason Kelly, Fahima Ahmady, Fadi Charchar" is provided in this record**
- Authors: Wang, Yutang , Nguyen, Dinh , Anesi, Jack , Kelly, Jason , Ahmady, Fahima , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Assay and Drug Development Technologies Vol. 19, no. 3 (2021), p. 184-190. https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay is one of the most commonly used tests of cell proliferation. Hydralazine has been reported to interfere with the performance of the MTS assay when used on adherent cells. This study aimed to investigate whether hydralazine interferes with the performance of the MTS assay on suspended cells. THP-1 (a monocytic leukemia cell line) cells were cultured in the presence or absence of hydralazine (0, 10, 50, 100, and 500 μM) for 2 or 24 h. Cell numbers were analyzed using the MTS, trypan blue exclusion, or microscopic assays. A modified version of the standard MTS assay was established by centrifuging the cells and replacing the test medium with fresh culture medium immediately before the addition of the MTS reagent. Culture of THP-1 cells with hydralazine at concentrations of 50, 100, and 500 μM for 2 h increased absorbance (p < 0.001) in the standard MTS assay, whereas both the trypan blue exclusion assay and microscopy suggested no change in cell numbers. Culture of THP-1 cells with 100 and 500 μm hydralazine for 24 h increased absorbance (p < 0.05) in the standard MTS assay; however, trypan blue exclusion and microscopy suggested a decrease in cell numbers. In a cell-free system, hydralazine (100 and 500 μM) increased absorbance in a time- and concentration-dependent manner. The modified MTS assay produced results consistent with trypan blue exclusion and microscopy using THP-1 cells. In addition, the modified MTS assay produced reliable results when K562 and Jurkat cells were incubated with hydralazine or β-mercaptoethanol (βME). In conclusion, a simple modification of the standard MTS assay overcame the interference of hydralazine and βME when assessing suspended cells. © Copyright 2021, Mary Ann Liebert, Inc., publishers 2021. *Please note that there are multiple authors for this article therefore only the name of the Federation University Australia affiliates “Yutang Wang, Dinh Nguyen, Jack Anesi, Jason Kelly, Fahima Ahmady, Fadi Charchar" is provided in this record**
Establishment of sex difference in circulating uric acid is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys
- Wang, Yutang, Charchar, Fadi
- Authors: Wang, Yutang , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Men have higher circulating levels of uric acid than women. This sex difference is suspected to be a result of suppressive effects of estradiol on uric acid. If so, estradiol would be inversely associated with circulating uric acid. This study aimed to test this hypothesis. This cross-sectional study included 9472 participants (weighted sample size of 184,342,210) aged 12–80 years from the 2013 to 2016 US National Health and Nutrition Examination Survey. Associations of sex hormones with uric acid were analyzed using weighted least squares regression, adjusting for demographic characteristics, lifestyle risk factors, and comorbidities. Neither free nor bioavailable estradiol was inversely associated with circulating uric acid in adolescent boys or girls, or adult men or women, or perimenopausal women after full adjustment. The sex difference in uric acid was established during adolescence as a result of a dramatic increase in uric acid in adolescent boys. During adolescence, the increase in estradiol in girls over time was accompanied by a relatively unchanged level of uric acid. All three fractions of estradiol (free, bioavailable, and total) were positively associated with uric acid in adolescent boys and girls after full adjustment. In adolescent boys, all three fractions of testosterone were positively associated with serum uric acid, and sex hormone-binding globulin was inversely associated with uric acid after full adjustment. These results suggest that estradiol is not inversely associated with circulating uric acid in adolescents and the establishment of sex difference in circulating uric acid during adolescence is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys. © 2021, The Author(s).
- Authors: Wang, Yutang , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 11, no. 1 (2021), p.
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Men have higher circulating levels of uric acid than women. This sex difference is suspected to be a result of suppressive effects of estradiol on uric acid. If so, estradiol would be inversely associated with circulating uric acid. This study aimed to test this hypothesis. This cross-sectional study included 9472 participants (weighted sample size of 184,342,210) aged 12–80 years from the 2013 to 2016 US National Health and Nutrition Examination Survey. Associations of sex hormones with uric acid were analyzed using weighted least squares regression, adjusting for demographic characteristics, lifestyle risk factors, and comorbidities. Neither free nor bioavailable estradiol was inversely associated with circulating uric acid in adolescent boys or girls, or adult men or women, or perimenopausal women after full adjustment. The sex difference in uric acid was established during adolescence as a result of a dramatic increase in uric acid in adolescent boys. During adolescence, the increase in estradiol in girls over time was accompanied by a relatively unchanged level of uric acid. All three fractions of estradiol (free, bioavailable, and total) were positively associated with uric acid in adolescent boys and girls after full adjustment. In adolescent boys, all three fractions of testosterone were positively associated with serum uric acid, and sex hormone-binding globulin was inversely associated with uric acid after full adjustment. These results suggest that estradiol is not inversely associated with circulating uric acid in adolescents and the establishment of sex difference in circulating uric acid during adolescence is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys. © 2021, The Author(s).
An improved 3-(4,5-dmethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl )-2H-tetrazolium proliferation assay to overcome the interference of hydralazine
- Wang, Yutang, Nguyen, Dinh, Yang, Guang, Anesi, Jack, Chai, Zhonglin, Charchar, Fadi, Golledge, Jonathan
- Authors: Wang, Yutang , Nguyen, Dinh , Yang, Guang , Anesi, Jack , Chai, Zhonglin , Charchar, Fadi , Golledge, Jonathan
- Date: 2020
- Type: Text , Journal article
- Relation: Assay and Drug Development Technologies Vol. 18, no. 8 (Dec 2020), p. 379-384
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: The MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay is one of the most commonly used assays to assess cell proliferation and cytotoxicity, but is subject to interference by testing compounds. Hydralazine, an antihypertensive drug, is commonly investigated in multiple fields such as heart failure, cancer, and blood pressure research. This study reported interference of the MTS assay by hydralazine and a simple modification overcoming this interference. Vascular smooth muscle cells were cultured in the presence or absence of hydralazine (0, 10, 50,100, and 500 mu M) for 2 or 24 h. Cell numbers were analyzed using MTS, trypan blue exclusion, or microscopic assays. A modified version of the standard MTS assay was established, in which an additional step was added replacing the test medium, containing hydralazine, with fresh culture medium immediately before the addition of the MTS reagent. Culture with hydralazine at concentrations of 50, 100, and 500 mu M for 2 h increased absorbance (p< 0.05) in the standard MTS assay, whereas microscopy suggested no change in cell numbers. Culture with 500 mu m hydralazine for 24 h increased absorbance (p< 0.05) in the standard MTS assay, however, trypan blue exclusion and microscopy suggested a decrease in cell numbers. In a cell-free system, hydralazine (>= 10 mu M) increased absorbance in a concentration-dependent manner. The modified MTS assay produced results consistent with trypan blue exclusion and microscopy. In conclusion, a simple modification of the standard MTS assay overcame the interference of hydralazine and may be useful to avoid interference from other tested compounds.
- Authors: Wang, Yutang , Nguyen, Dinh , Yang, Guang , Anesi, Jack , Chai, Zhonglin , Charchar, Fadi , Golledge, Jonathan
- Date: 2020
- Type: Text , Journal article
- Relation: Assay and Drug Development Technologies Vol. 18, no. 8 (Dec 2020), p. 379-384
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: The MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay is one of the most commonly used assays to assess cell proliferation and cytotoxicity, but is subject to interference by testing compounds. Hydralazine, an antihypertensive drug, is commonly investigated in multiple fields such as heart failure, cancer, and blood pressure research. This study reported interference of the MTS assay by hydralazine and a simple modification overcoming this interference. Vascular smooth muscle cells were cultured in the presence or absence of hydralazine (0, 10, 50,100, and 500 mu M) for 2 or 24 h. Cell numbers were analyzed using MTS, trypan blue exclusion, or microscopic assays. A modified version of the standard MTS assay was established, in which an additional step was added replacing the test medium, containing hydralazine, with fresh culture medium immediately before the addition of the MTS reagent. Culture with hydralazine at concentrations of 50, 100, and 500 mu M for 2 h increased absorbance (p< 0.05) in the standard MTS assay, whereas microscopy suggested no change in cell numbers. Culture with 500 mu m hydralazine for 24 h increased absorbance (p< 0.05) in the standard MTS assay, however, trypan blue exclusion and microscopy suggested a decrease in cell numbers. In a cell-free system, hydralazine (>= 10 mu M) increased absorbance in a concentration-dependent manner. The modified MTS assay produced results consistent with trypan blue exclusion and microscopy. In conclusion, a simple modification of the standard MTS assay overcame the interference of hydralazine and may be useful to avoid interference from other tested compounds.
Fasting triglycerides are positively associated with cardiovascular mortality risk in people with diabetes
- Wang, Yutang, Fang, Yan, Magliano, Dianna, Charchar, Fadi, Sobey, Christopher, Drummond, Grant, Golledge, Jonathan
- Authors: Wang, Yutang , Fang, Yan , Magliano, Dianna , Charchar, Fadi , Sobey, Christopher , Drummond, Grant , Golledge, Jonathan
- Date: 2023
- Type: Text , Journal article
- Relation: Cardiovascular Research Vol. 119, no. 3 (2023), p. 826-834
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Aims We investigated the association of fasting triglycerides with cardiovascular disease (CVD) mortality. Methods and results This cohort study included US adults from the National Health and Nutrition Examination Surveys from 1988 to 2014. CVD mortality outcomes were ascertained by linkage to the National Death Index records. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of triglycerides for CVD mortality. The cohort included 26 570 adult participants, among which 3978 had diabetes. People with higher triglycerides had a higher prevalence of diabetes at baseline. The cohort was followed up for a mean of 12.0 years with 1492 CVD deaths recorded. A 1-natural-log-unit higher triglyceride was associated with a 30% higher multivariate-adjusted risk of CVD mortality in participants with diabetes (HR, 1.30; 95% CI, 1.08–1.56) but not in those without diabetes (HR, 0.95; 95% CI, 0.83–1.07). In participants with diabetes, people with high triglycerides (200–499 mg/dL) had a 44% (HR, 1.44; 95% CI, 1.12–1.85) higher multivariate-adjusted risk of CVD mortality compared with those with normal triglycerides (<150 mg/dL). The findings remained significant when diabetes was defined by fasting glucose levels alone, or after further adjustment for the use of lipid-lowering medications, or after the exclusion of those who took lipid-lowering medications. Conclusion This study demonstrates that fasting triglycerides of
- Authors: Wang, Yutang , Fang, Yan , Magliano, Dianna , Charchar, Fadi , Sobey, Christopher , Drummond, Grant , Golledge, Jonathan
- Date: 2023
- Type: Text , Journal article
- Relation: Cardiovascular Research Vol. 119, no. 3 (2023), p. 826-834
- Relation: https://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Aims We investigated the association of fasting triglycerides with cardiovascular disease (CVD) mortality. Methods and results This cohort study included US adults from the National Health and Nutrition Examination Surveys from 1988 to 2014. CVD mortality outcomes were ascertained by linkage to the National Death Index records. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of triglycerides for CVD mortality. The cohort included 26 570 adult participants, among which 3978 had diabetes. People with higher triglycerides had a higher prevalence of diabetes at baseline. The cohort was followed up for a mean of 12.0 years with 1492 CVD deaths recorded. A 1-natural-log-unit higher triglyceride was associated with a 30% higher multivariate-adjusted risk of CVD mortality in participants with diabetes (HR, 1.30; 95% CI, 1.08–1.56) but not in those without diabetes (HR, 0.95; 95% CI, 0.83–1.07). In participants with diabetes, people with high triglycerides (200–499 mg/dL) had a 44% (HR, 1.44; 95% CI, 1.12–1.85) higher multivariate-adjusted risk of CVD mortality compared with those with normal triglycerides (<150 mg/dL). The findings remained significant when diabetes was defined by fasting glucose levels alone, or after further adjustment for the use of lipid-lowering medications, or after the exclusion of those who took lipid-lowering medications. Conclusion This study demonstrates that fasting triglycerides of
Dietary fatty acids and mortality risk from heart disease in US adults : an analysis based on NHANES
- Wang, Yutang, Fang, Yan, Witting, Paul, Charchar, Fadi, Sobey, Christopher, Drummond, Grant, Golledge, Jonothan
- Authors: Wang, Yutang , Fang, Yan , Witting, Paul , Charchar, Fadi , Sobey, Christopher , Drummond, Grant , Golledge, Jonothan
- Date: 2023
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 13, no. 1 (2023), p.
- Full Text:
- Reviewed:
- Description: We investigated the association of dietary intake of major types of fatty acids with heart disease mortality in a general adult cohort with or without a prior diagnosis of myocardial infarction (MI). This cohort study included US adults who attended the National Health and Nutrition Examination Surveys from 1988 to 2014. Heart disease mortality was ascertained by linkage to the National Death Index records through 31 December 2015. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of fatty acid intake for heart disease mortality. This cohort included 45,820 adults among which 1,541 had a prior diagnosis of MI. Participants were followed up for 532,722 person-years (mean follow-up, 11.6 years), with 2,313 deaths recorded from heart disease being recorded. Intake of saturated (SFAs) and monounsaturated fatty acids (MUFAs) was associated with heart disease mortality after adjustment for all the tested confounders. In contrast, a 5% higher calorie intake from polyunsaturated fatty acids (PUFAs) was associated with a 9% (HR, 0.91; 95% CI 0.83–1.00; P = 0.048) lower multivariate-adjusted risk of heart disease mortality. Sub-analyses showed that this inverse association was present in those without a prior diagnosis of MI (HR,0.89; 95% CI 0.80–0.99) but not in those with the condition (HR, 0.94; 95% CI 0.75–1.16). The lack of association in the MI group could be due to a small sample size or severity and procedural complications (e.g., stenting and medication adherence) of the disease. Higher PUFA intake was associated with a favourable lipid profile. However, further adjustment for plasma lipids did not materially change the inverse association between PUFAs and heart disease mortality. Higher intake of PUFAs, but not SFAs and MUFAs, was associated with a lower adjusted risk of heart disease mortality in a large population of US adults supporting the need to increase dietary PUFA intake in the general public. © 2023, The Author(s).
Dietary fatty acids and mortality risk from heart disease in US adults : an analysis based on NHANES
- Authors: Wang, Yutang , Fang, Yan , Witting, Paul , Charchar, Fadi , Sobey, Christopher , Drummond, Grant , Golledge, Jonothan
- Date: 2023
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 13, no. 1 (2023), p.
- Full Text:
- Reviewed:
- Description: We investigated the association of dietary intake of major types of fatty acids with heart disease mortality in a general adult cohort with or without a prior diagnosis of myocardial infarction (MI). This cohort study included US adults who attended the National Health and Nutrition Examination Surveys from 1988 to 2014. Heart disease mortality was ascertained by linkage to the National Death Index records through 31 December 2015. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of fatty acid intake for heart disease mortality. This cohort included 45,820 adults among which 1,541 had a prior diagnosis of MI. Participants were followed up for 532,722 person-years (mean follow-up, 11.6 years), with 2,313 deaths recorded from heart disease being recorded. Intake of saturated (SFAs) and monounsaturated fatty acids (MUFAs) was associated with heart disease mortality after adjustment for all the tested confounders. In contrast, a 5% higher calorie intake from polyunsaturated fatty acids (PUFAs) was associated with a 9% (HR, 0.91; 95% CI 0.83–1.00; P = 0.048) lower multivariate-adjusted risk of heart disease mortality. Sub-analyses showed that this inverse association was present in those without a prior diagnosis of MI (HR,0.89; 95% CI 0.80–0.99) but not in those with the condition (HR, 0.94; 95% CI 0.75–1.16). The lack of association in the MI group could be due to a small sample size or severity and procedural complications (e.g., stenting and medication adherence) of the disease. Higher PUFA intake was associated with a favourable lipid profile. However, further adjustment for plasma lipids did not materially change the inverse association between PUFAs and heart disease mortality. Higher intake of PUFAs, but not SFAs and MUFAs, was associated with a lower adjusted risk of heart disease mortality in a large population of US adults supporting the need to increase dietary PUFA intake in the general public. © 2023, The Author(s).
- Veerabhadrappa, Praveen, Burger, Dylan, Charchar, Fadi, Tomaszewski, Maciej, Carlberg, Bo, Harrap, Stephen, Touyz, Rhian
- Authors: Veerabhadrappa, Praveen , Burger, Dylan , Charchar, Fadi , Tomaszewski, Maciej , Carlberg, Bo , Harrap, Stephen , Touyz, Rhian
- Date: 2012
- Type: Text , Journal article
- Relation: Hypertension Vol. 59, no. 2 SUPPL. 1 (2012), p. 382-383
- Full Text: false
- Reviewed:
Leading the change: Second International Society of Hypertension New Investigators' Symposium
- Veerabhadrappa, Praveen, Charchar, Fadi, Burger, Dylan, Tomaszewski, Maciej, Carlberg, Bo
- Authors: Veerabhadrappa, Praveen , Charchar, Fadi , Burger, Dylan , Tomaszewski, Maciej , Carlberg, Bo
- Date: 2013
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 31, no. 2 (February 2013), p. 429-430
- Full Text: false
- Reviewed:
ISH Hypertension Future Leaders Group : A network for new investigators run by new investigators
- Veerabhadrappa, Praveen, Burger, Dylan, Carlberg, Bo, Charchar, Fadi, Tomaszewski, Maciej, Harrap, Stephen, Horsfield, Helen
- Authors: Veerabhadrappa, Praveen , Burger, Dylan , Carlberg, Bo , Charchar, Fadi , Tomaszewski, Maciej , Harrap, Stephen , Horsfield, Helen
- Date: 2011
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 29, no. 8 (2011), p. 1664-1665
- Full Text: false
- Reviewed:
2020 International Society of Hypertension global hypertension practice guidelines
- Unger, Thomas, Borghi, Claudio, Charchar, Fadi, Khan, Nadia, Poulter, Neil, Prabhakaran, Dorairaj, Ramirez, Agustin, Schlaich, Markus, Stergiou, George, Tomaszewski, Maciej, Wainford, Richard, Williams, Bryan, Schutte, Aletta
- Authors: Unger, Thomas , Borghi, Claudio , Charchar, Fadi , Khan, Nadia , Poulter, Neil , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Stergiou, George , Tomaszewski, Maciej , Wainford, Richard , Williams, Bryan , Schutte, Aletta
- Date: 2020
- Type: Text , Journal article
- Relation: Journal of hypertension Vol. 38, no. 6 (2020), p. 982-1004
- Full Text:
- Reviewed:
- Description: DOCUMENT REVIEWERS: Hind Beheiry (Sudan), Irina Chazova (Russia), Albertino Damasceno (Mozambique), Anna Dominiczak (UK), Anastase Dzudie (Cameroon), Stephen Harrap (Australia), Hiroshi Itoh (Japan), Tazeen Jafar (Singapore), Marc Jaffe (USA), Patricio Jaramillo-Lopez (Colombia), Kazuomi Kario (Japan), Giuseppe Mancia (Italy), Ana Mocumbi (Mozambique), Sanjeevi N.Narasingan (India), Elijah Ogola (Kenya), Srinath Reddy (India), Ernesto Schiffrin (Canada), Ann Soenarta (Indonesia), Rhian Touyz (UK), Yudah Turana (Indonesia), Michael Weber (USA), Paul Whelton (USA), Xin Hua Zhang, (Australia), Yuqing Zhang (China).
- Authors: Unger, Thomas , Borghi, Claudio , Charchar, Fadi , Khan, Nadia , Poulter, Neil , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Stergiou, George , Tomaszewski, Maciej , Wainford, Richard , Williams, Bryan , Schutte, Aletta
- Date: 2020
- Type: Text , Journal article
- Relation: Journal of hypertension Vol. 38, no. 6 (2020), p. 982-1004
- Full Text:
- Reviewed:
- Description: DOCUMENT REVIEWERS: Hind Beheiry (Sudan), Irina Chazova (Russia), Albertino Damasceno (Mozambique), Anna Dominiczak (UK), Anastase Dzudie (Cameroon), Stephen Harrap (Australia), Hiroshi Itoh (Japan), Tazeen Jafar (Singapore), Marc Jaffe (USA), Patricio Jaramillo-Lopez (Colombia), Kazuomi Kario (Japan), Giuseppe Mancia (Italy), Ana Mocumbi (Mozambique), Sanjeevi N.Narasingan (India), Elijah Ogola (Kenya), Srinath Reddy (India), Ernesto Schiffrin (Canada), Ann Soenarta (Indonesia), Rhian Touyz (UK), Yudah Turana (Indonesia), Michael Weber (USA), Paul Whelton (USA), Xin Hua Zhang, (Australia), Yuqing Zhang (China).
2020 International Society of Hypertension global hypertension practice guidelines
- Unger, Thomas, Borghi, Claudio, Charchar, Fadi, Khan, Nadia, Poulter, Neil, Prabhakaran, Dorairaj, Ramirez, Agustin, Schlaich, Markus, Stergiou, George, Wainford, Richard, Williams, Bryan, Schutte, Aletta
- Authors: Unger, Thomas , Borghi, Claudio , Charchar, Fadi , Khan, Nadia , Poulter, Neil , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Stergiou, George , Wainford, Richard , Williams, Bryan , Schutte, Aletta
- Date: 2020
- Type: Text , Journal article
- Relation: Hypertension Vol. 75, no. 6 (2020), p. 1334-1357
- Full Text:
- Reviewed:
- Authors: Unger, Thomas , Borghi, Claudio , Charchar, Fadi , Khan, Nadia , Poulter, Neil , Prabhakaran, Dorairaj , Ramirez, Agustin , Schlaich, Markus , Stergiou, George , Wainford, Richard , Williams, Bryan , Schutte, Aletta
- Date: 2020
- Type: Text , Journal article
- Relation: Hypertension Vol. 75, no. 6 (2020), p. 1334-1357
- Full Text:
- Reviewed:
- Tomaszewski, Maciej, Charchar, Fadi, Barnes, Timothy, Gawron-Kiszka, Magdalena, Sedkowska, Agnieszka, Podolecka, Ewa, Kowalczyk, Jacek, Rathbone, Wendy, Kalarus, Zbigniew, Grzeszczak, Wladyslaw, Goodall, Alison, Samani, Nilesh, Zukowska-Szczechowska, Ewa
- Authors: Tomaszewski, Maciej , Charchar, Fadi , Barnes, Timothy , Gawron-Kiszka, Magdalena , Sedkowska, Agnieszka , Podolecka, Ewa , Kowalczyk, Jacek , Rathbone, Wendy , Kalarus, Zbigniew , Grzeszczak, Wladyslaw , Goodall, Alison , Samani, Nilesh , Zukowska-Szczechowska, Ewa
- Date: 2009
- Type: Text , Journal article
- Relation: Arteriosclerosis Thrombosis and Vascular Biology Vol. 29, no. 9 (2009), p. 1316-1321
- Full Text: false
- Reviewed:
- Description: Objective-A rare mutation in low-density lipoprotein receptor-related protein 6 gene (LRP6) was identified as the primary molecular defect underlying monogenic form of coronary artery disease. We hypothesized that common variants in LRP6 could predispose subjects to elevated LDL-cholesterol (LDL-C). Methods and Results-Twelve common ( minor allele frequency >= 0.1) single nucleotide polymorphisms in LRP6 were genotyped in 703 individuals from 213 Polish pedigrees (Silesian Cardiovascular Study families). The family-based analysis revealed that the minor allele of rs10845493 clustered with elevated LDL-C in offspring more frequently than expected by chance (P=0.0053). The quantitative analysis restricted to subjects free of lipid-lowering treatment confirmed the association between rs10845493 and age-, sex-, and BMI-adjusted circulating levels of LDL-C in families as well as 2 additional populations - 218 unrelated subjects from Silesian Cardiovascular Study replication panel and 1138 individuals from Young Men Cardiovascular Association cohort (P=0.0268, P=0.0476, and P=0.0472, respectively). In the inverse variance weighted meta-analysis of the 3 populations each extra minor allele copy of rs10845493 was associated with 0.14 mmol/L increase in age-, sex-, and BMI-adjusted LDL-C (SE=0.05, P=0.0038). Conclusions-Common polymorphism in the gene underlying monogenic form of coronary artery disease impacts on risk of LDL-C elevation. (Arterioscler Thromb Vasc Biol. 2009;29:1316-1321.)
Cardiovascular diseases and G-protein beta 3 subunit gene (GNB3) in the era of genomewide scans
- Tomaszewski, Maciej, Charchar, Fadi, Padmanabhan, Sandosh, Zukowska-Szczechowska, Ewa, Grzeszczak, Wladyslaw, Dominiczak, Anna
- Authors: Tomaszewski, Maciej , Charchar, Fadi , Padmanabhan, Sandosh , Zukowska-Szczechowska, Ewa , Grzeszczak, Wladyslaw , Dominiczak, Anna
- Date: 2003
- Type: Text , Journal article
- Relation: Journal of Human Hypertension Vol. 17, no. 6 (2003), p. 379-380
- Full Text: false
- Reviewed:
- Tomaszewski, Maciej, Charchar, Fadi, Barnes, Timothy, Gawron-Kiszka, Magdalena, Sedkowska, Agnieszka, Grzeszczak, Wladyslaw, Samani, Nilesh, Zukowska-Szczechowska, Ewa
- Authors: Tomaszewski, Maciej , Charchar, Fadi , Barnes, Timothy , Gawron-Kiszka, Magdalena , Sedkowska, Agnieszka , Grzeszczak, Wladyslaw , Samani, Nilesh , Zukowska-Szczechowska, Ewa
- Date: 2008
- Type: Text , Journal article
- Relation: Hypertension Vol. 52, no. 4 (Oct 2008), p. E129-E129
- Full Text: false
- Reviewed:
- Description: C1
- Tomaszewski, Maciej, Charchar, Fadi, Barnes, Timothy, Maric, Christine, Zukowska-Szczechowska, Ewa, Samani, Nilesh
- Authors: Tomaszewski, Maciej , Charchar, Fadi , Barnes, Timothy , Maric, Christine , Zukowska-Szczechowska, Ewa , Samani, Nilesh
- Date: 2010
- Type: Text , Conference paper
- Relation: Paper presented at British Cardiovascular Society Annual Conference 2010, Manchester Central, Manchester, UK : 7th-9th June 2010
- Full Text: false
- Description: Essential hypertension is a complex, multifactorial disease with a strong genetic component. Fibroblast growth factor 1 gene (FGF1) is one of the most relevant candidates having been associated not only with familial susceptibility to hypertension but also with up-regulation within the glomerulus of the human hypertensive kidney/Circulation 2007;116:1915e24/. We have hypothesised that systematic analysis of genes interacting with FGF1 may uncover novel variants underlying essential hypertension. Seventy-nine common (minor allele frequency$0.1) tagging (r2$0.8) and functional single nucleotide polymorphisms (SNPs) spanning eight critical components of the FGF (fibroblast growth factor) pathway (FGF2, FGFR1, FGFR2, FGFR3, FGFR4, FGFBP1, FIBP, SPRY1) were genotyped by MALDI-TOF mass spectrometry in 629 subjects from 207 Polish hypertensive families (Silesian Hypertension Study d SHS). 83.5% of genotyped SNPs that passed quality control filters provided 92.9% genetic coverage of FGF pathway loci. Family-based analysis in SHS revealed that alleles of three SNPs (rs2956724, rs2245964 and rs16892645) in two loci (FGFR1 and FGFBP1) were transmitted to hypertensive offspring more frequently than expected by chance. However, only one association survived correction for multiple testing e major allele of rs16892645 in FGFBP1 was over-transmitted from heterozygous parents to hypertensive offspring more frequently than expected by chance (p¼0.0048, false discovery rate<0.25). The association between rs16892645 and hypertension was replicated in an independent cohort of 807 Polish subjects from Silesian Cardiovascular Study d each major allele copy of rs16892645 increased the odds of hypertension approximately by 1.5 (odds ratio: 1.5; 95% CI: 1.1 to to 2.2, p¼0.04). Association between FGFBP1 and hypertension was also apparent at the protein expression level d compared with normotensive patients, hypertensives from Silesian Renal Tissue Bank showed approximately 1.4-fold higher renal abundance of FGFBP1 in Western blotting (p¼0.001). Immunohistochemical analysis revealed that hypertension-related up-regulation of FGFBP1 was exclusive to renal glomeruli. These data show that FGFBP1da gene that encodes a carrier protein for FGF1 d is associated with human hypertension. We also reveal that up-regulation of FGFBP1 maps to the same histological compartment where FGF1 was shown to be most abundant (renal glomeruli). Our study also proves that systematic genetic analysis of signalling pathways is a strategy with a potential to identify novel molecular mechanisms underlying blood pressure elevation.