Human Y Chromosome Exerts Pleiotropic Effects on Susceptibility to Atherosclerosis
- Eales, James, Maan, Akhlaq, Xu, Xiaoguang, Michoel, Tom, Hallast, Pille, Batini, C, Zadik, Daniel, Prestes, Priscilla, Molina, Elsa, Denniff, Matthew, Schroeder, Juliane, Bjorkegren, Johan, Thompson, John, Maffia, Pasquale, Guzik, Tomasz, Keavney, Bernard, Jobling, Mark, Samani, Nilesh, Charchar, Fadi, Tomaszewski, Maciej
- Authors: Eales, James , Maan, Akhlaq , Xu, Xiaoguang , Michoel, Tom , Hallast, Pille , Batini, C , Zadik, Daniel , Prestes, Priscilla , Molina, Elsa , Denniff, Matthew , Schroeder, Juliane , Bjorkegren, Johan , Thompson, John , Maffia, Pasquale , Guzik, Tomasz , Keavney, Bernard , Jobling, Mark , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2019
- Type: Text , Journal article
- Relation: Arteriosclerosis, thrombosis, and vascular biology Vol. 39, no. 11 (2019), p. 2386-2401
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- Description: OBJECTIVE: The male-specific region of the Y chromosome (MSY) remains one of the most unexplored regions of the genome. We sought to examine how the genetic variants of the MSY influence male susceptibility to coronary artery disease (CAD) and atherosclerosis. Approach and Results: Analysis of 129 133 men from UK Biobank revealed that only one of 7 common MSY haplogroups (haplogroup I1) was associated with CAD-carriers of haplogroup I1 had ≈11% increase in risk of CAD when compared with all other haplogroups combined (odds ratio, 1.11; 95% CI, 1.04-1.18; P=6.8×10-4). Targeted MSY sequencing uncovered 235 variants exclusive to this haplogroup. The haplogroup I1-specific variants showed 2.45- and 1.56-fold respective enrichment for promoter and enhancer chromatin states, in cells/tissues relevant to atherosclerosis, when compared with other MSY variants. Gene set enrichment analysis in CAD-relevant tissues showed that haplogroup I1 was associated with changes in pathways responsible for early and late stages of atherosclerosis development including defence against pathogens, immunity, oxidative phosphorylation, mitochondrial respiration, lipids, coagulation, and extracellular matrix remodeling. UTY was the only Y chromosome gene whose blood expression was associated with haplogroup I1. Experimental reduction of UTY expression in macrophages led to changes in expression of 59 pathways (28 of which overlapped with those associated with haplogroup I1) and a significant reduction in the immune costimulatory signal. CONCLUSIONS: Haplogroup I1 is enriched for regulatory chromatin variants in numerous cells of relevance to CAD and increases cardiovascular risk through proatherosclerotic reprogramming of the transcriptome, partly through UTY.
- Authors: Eales, James , Maan, Akhlaq , Xu, Xiaoguang , Michoel, Tom , Hallast, Pille , Batini, C , Zadik, Daniel , Prestes, Priscilla , Molina, Elsa , Denniff, Matthew , Schroeder, Juliane , Bjorkegren, Johan , Thompson, John , Maffia, Pasquale , Guzik, Tomasz , Keavney, Bernard , Jobling, Mark , Samani, Nilesh , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2019
- Type: Text , Journal article
- Relation: Arteriosclerosis, thrombosis, and vascular biology Vol. 39, no. 11 (2019), p. 2386-2401
- Full Text:
- Reviewed:
- Description: OBJECTIVE: The male-specific region of the Y chromosome (MSY) remains one of the most unexplored regions of the genome. We sought to examine how the genetic variants of the MSY influence male susceptibility to coronary artery disease (CAD) and atherosclerosis. Approach and Results: Analysis of 129 133 men from UK Biobank revealed that only one of 7 common MSY haplogroups (haplogroup I1) was associated with CAD-carriers of haplogroup I1 had ≈11% increase in risk of CAD when compared with all other haplogroups combined (odds ratio, 1.11; 95% CI, 1.04-1.18; P=6.8×10-4). Targeted MSY sequencing uncovered 235 variants exclusive to this haplogroup. The haplogroup I1-specific variants showed 2.45- and 1.56-fold respective enrichment for promoter and enhancer chromatin states, in cells/tissues relevant to atherosclerosis, when compared with other MSY variants. Gene set enrichment analysis in CAD-relevant tissues showed that haplogroup I1 was associated with changes in pathways responsible for early and late stages of atherosclerosis development including defence against pathogens, immunity, oxidative phosphorylation, mitochondrial respiration, lipids, coagulation, and extracellular matrix remodeling. UTY was the only Y chromosome gene whose blood expression was associated with haplogroup I1. Experimental reduction of UTY expression in macrophages led to changes in expression of 59 pathways (28 of which overlapped with those associated with haplogroup I1) and a significant reduction in the immune costimulatory signal. CONCLUSIONS: Haplogroup I1 is enriched for regulatory chromatin variants in numerous cells of relevance to CAD and increases cardiovascular risk through proatherosclerotic reprogramming of the transcriptome, partly through UTY.
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
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- 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).
The differences in the prevalence of cardiovascular disease, its risk factors, and achievement of therapeutic goals among urban and rural primary care patients in Poland: Results from the LIPIDOGRAM 2015 study
- Studziński, Krzysztof, Tomasik, Tomasz, Windak, Adam, Banach, Maciej, Charchar, Fadi
- Authors: Studziński, Krzysztof , Tomasik, Tomasz , Windak, Adam , Banach, Maciej , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of Clinical Medicine Vol. 10, no. 23 (2021), p.
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- Description: A nationwide cross-sectional study, LIPIDOGRAM2015, was carried out in Poland in the years 2015 and 2016. A total of 438 primary care physicians enrolled 13,724 adult patients that sought medical care in primary health care practices. The prevalence of hypertension, diabetes mellitus, dyslipidaemia, and CVD were similar in urban and rural areas (49.5 vs. 49.4%; 13.7 vs. 13.1%; 84.2 vs. 85.2%; 14.4 vs. 14.2%, respectively). The prevalence of obesity (32.3 vs. 37.5%, p < 0.01) and excessive waist circumference (77.5 vs. 80.7%, p < 0.01), as well as abdominal obesity (p = 43.2 vs. 46.4%, p < 0.01), were higher in rural areas in both genders. Mean levels of LDL-C (128 vs. 130 mg/dL, p = 0.04) and non-HDL-C (147 vs. 148 mg/dL, p = 0.03) were slightly higher in rural populations. Altogether, 14.3% of patients with CVD from urban areas and 11.3% from rural areas reached LDL <70 mg/dL (p = 0.04). There were no important differences in the prevalence of hypertension, diabetes, dyslipidaemia, and CVD, or in mean levels of blood pressure, cholesterol fractions, glucose, and HbA1c between Polish urban and rural primary care patient populations. A high proportion of patients in cities and an even-higher proportion in rural areas did not reach the recommended targets for blood pressure, LDL-C, and HbA1c, indicating the need for novel CVD-prevention programs. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
- Authors: Studziński, Krzysztof , Tomasik, Tomasz , Windak, Adam , Banach, Maciej , Charchar, Fadi
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of Clinical Medicine Vol. 10, no. 23 (2021), p.
- Full Text:
- Reviewed:
- Description: A nationwide cross-sectional study, LIPIDOGRAM2015, was carried out in Poland in the years 2015 and 2016. A total of 438 primary care physicians enrolled 13,724 adult patients that sought medical care in primary health care practices. The prevalence of hypertension, diabetes mellitus, dyslipidaemia, and CVD were similar in urban and rural areas (49.5 vs. 49.4%; 13.7 vs. 13.1%; 84.2 vs. 85.2%; 14.4 vs. 14.2%, respectively). The prevalence of obesity (32.3 vs. 37.5%, p < 0.01) and excessive waist circumference (77.5 vs. 80.7%, p < 0.01), as well as abdominal obesity (p = 43.2 vs. 46.4%, p < 0.01), were higher in rural areas in both genders. Mean levels of LDL-C (128 vs. 130 mg/dL, p = 0.04) and non-HDL-C (147 vs. 148 mg/dL, p = 0.03) were slightly higher in rural populations. Altogether, 14.3% of patients with CVD from urban areas and 11.3% from rural areas reached LDL <70 mg/dL (p = 0.04). There were no important differences in the prevalence of hypertension, diabetes, dyslipidaemia, and CVD, or in mean levels of blood pressure, cholesterol fractions, glucose, and HbA1c between Polish urban and rural primary care patient populations. A high proportion of patients in cities and an even-higher proportion in rural areas did not reach the recommended targets for blood pressure, LDL-C, and HbA1c, indicating the need for novel CVD-prevention programs. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Fadi Charchar” is provided in this record**
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