Cardiovascular diseases and G-protein beta 3 subunit gene (GNB3) in the era of genomewide scans
- 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
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Strikingly low circulating CRP concentrations in ultramarathon runners independent of markers of adiposity - How low can you go?
- Authors: Tomaszewski, Maciej , Charchar, Fadi , Przybycin, Malgorzata , Crawford, Lynne , Wallace, A. Michael. , Gosek, Katarzyna , Lowe, Gordon. D. , Zukowska-Szczechowska, Ewa , Grzeszczak, Wladyslaw , Sattar, Naveed , Dominiczak, Anna
- Date: 2003
- Type: Text , Journal article
- Relation: Arteriosclerosis Thrombosis and Vascular Biology Vol. 23, no. 9 (2003), p. 1640-1644
- Full Text: false
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- Description: Objective-This study was undertaken to evaluate to what extent C-reactive protein (CRP) can be reduced by exercise by examining its circulating concentrations in male ultramarathon runners and to determine if low leptin as a robust circulating marker of fat mass could account for low CRP in such men. Methods and Results-Sixty-seven male ultramarathon runners and 63 sedentary male controls of similar age and body mass index were recruited. CRP and leptin were measured by ELISA and radioimmunoassay, respectively. Median CRP concentration in lean (body mass index <25 kg/m(2)) marathon runners was less than half control median (0.4 [0.2 to 0.9] mg/L versus 0.9 [0.5 to 2.7] mg/L, P=0.0013) and, more strikingly, in nonlean runners was approximately 26% of control median (0.4 [0.3 to 0.8] mg/L versus 1.5 [0.9 to 2.5] mg/L, P=0.0002). Circulating leptin levels were also substantially lower in lean (45% less) and nonlean (63% less, both P=0.0001) ultramarathon runners. However, interleukin-6 levels were not different. Furthermore, leptin adjustment only minimally attenuated the case-control difference in CRP, suggesting that mechanisms other than fat mass reduction contribute to low concentrations of CRP in marathon runners. Conclusions-This study suggests that circulating CRP concentrations can be markedly suppressed, independently of total adiposity or indeed fat mass, by intense regular physical exercise.
Orthologues of GSTM expressed in human kidney
- Authors: Brosnan, Julia , Tomaszewski, Maciej , McBride, Martin , Charchar, Fadi , Lacka, Beata , Zukowska-Szczechowska, Ewa , Grzeszczak, Wladyslaw , Lee, Wai , Dominiczak, Anna
- Date: 2004
- Type: Text , Journal article
- Relation: Journal of Hypertension Vol. 22, no. Suppl. 1 (2004), p. S183
- Full Text: false
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Genetics of human essential hypertension - from single mutations to quantitative trait loci
- Authors: Tomaszewski, Maciej , Brain, Nick , Charchar, Fadi , Dominiczak, Anna
- Date: 2006
- Type: Text , Book chapter
- Relation: Molecular mechanisms in hypertension Chapter p. 241-247
- Full Text: false
- Description: 2003007414
Common allelic variant in the gene underlying rare monogenic form of coronary artery disease cosegregates with elevated LDL cholesterol in families with high cardiovascular risk
- 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
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- Description: C1
The pressure of finding human hypertension genes : New tools, old dilemmas
- Authors: Charchar, Fadi , Zimmerli, Lukas , Tomaszewski, Maciej
- Date: 2008
- Type: Text , Journal article
- Relation: Journal of Human Hypertension Vol. 22, no. (2008), p. 821–828
- Full Text: false
- Reviewed:
- Description: Researchers in hypertension genetics feel like they are left behind again. It always seems that the 'other' complex diseases are ahead in the race. Evolving new technologies in the form of genome-wide arrays and 'omics' technologies mean that investigators can now potentially identify many novel disease factors in one large-scale experiment. Hypertension research now faces the challenge of where to go next after the first genome-wide association experiments failed to provide robust candidates. In this review, we contemplate the old dilemma of whether such genes may ever be found; however, we believe advancing technologies and plummeting costs of large-scale experiments will contribute to the identification of novel molecules that underlie essential hypertension.
Whole genome survey of copy number variation in the spontaneously hypertensive rat
- Authors: Charchar, Fadi , Samani, Nilesh
- Date: 2008
- Type: Text , Journal article
- Relation: Hypertension Vol. 52, no. 4 (Oct 2008), p. E100-E100
- Full Text: false
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- Description: C1
A common intronic variant in the gene underlying a rare monogenic form of coronary artery disease is associated with low-density lipoprotein cholesterol
- Authors: Tomaszewski, Maciej , Charchar, Fadi , Barnes, Timothy , Nasmith, W. E. , Grzeszczak, Wladyslaw , Zukowska-Szczechowska, Ewa , Samani, Nilesh
- Date: 2009
- Type: Text , Journal article
- Relation: Heart Vol. 95, no. (2009), p. A83-A83
- Full Text: false
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A common variant in low-density lipoprotein receptor-related protein 6 gene (LRP6) is associated with LDL-Cholesterol
- 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
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- 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.)
Association between lipid profile and circulating concentrations of estrogens in young men
- Authors: Tomaszewski, Maciej , Maric, Christine , Zuzniewicz, Roman , Gola, Mateusz , Grzeszczak, Wladyslaw , Samani, Nilesh , Zukowska-Szczechowska, Ewa , Charchar, Fadi
- Date: 2009
- Type: Text , Journal article
- Relation: Atheroclerosis Vol. 203, no. (2009), p. 257-262
- Full Text: false
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- Description: Objectives: Men show higher rates of cardiovascular morbidity and mortality than pre-menopausal women and this sexual dimorphism may be related to sex-specific effects of sex steroids on cardiovascular risk factors. Unlike androgens, estrogens were not extensively investigated in relation to cardiovascular phenotypes in men.
- Description: C1
Inverse associations between androgens and renal function : The Young Men Cardiovascular Association (YMCA) study
- Authors: Tomaszewski, Maciej , Charchar, Fadi , Maric, Christine , Kuzniewicz, Roman , Gola, Mateusz , Grzeszczak, Wladyslaw , Samani, Nilesh , Zukowska-Szczechowska, Ewa
- Date: 2009
- Type: Text , Journal article
- Relation: American Journal of Hypertension Vol. 22, no. 1 (2009), p. 100-105
- Full Text: false
- Reviewed:
- Description: Background: Men exhibit higher risk of nondiabetic renal diseases than women. This male susceptibility to renal disease may be mediated by gender-specific factors such as sex hormones. Methods: We have undertaken a cross-sectional examination of associations between renal function (creatinine clearance estimated based on Cockcroft-Gault equation) and circulating levels of sex steroids (total testosterone, total estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and dihydrotestosterone) in 928 young (mean age: 18.5 ± 1.2 years) men. Results: Both androstenedione and DHEA-S showed inverse linear associations with renal function in the crude analysis of lean men (those with body mass index (BMI) less than median). However, only DHEA-S retained its association with renal function in lean subjects after adjustment - assuming no changes in other independent variables 1 s.d. increase in DHEA-S was associated with 13%-s.d. decrease in creatinine clearance (P = 0.004). Testosterone decreased across tertiles of creatinine clearance only in the crude analysis of nonlean (BMI greater than median) subjects (P < 0.001). The adjusted regression analysis that assumed no changes in other independent variables showed that 1 s.d. increase in total testosterone was associated with 11%-s.d. decrease in creatinine clearance of nonlean men (P = 0.006). Factor analysis confirmed an inverse association of renal function with both sex steroids and a different pattern of their loadings on glomerular filtration-related factors in lean (DHEA-S) and nonlean (testosterone) subjects. Conclusions: Our data may suggest that androgens are inversely associated with estimated renal function in apparently healthy men without history of cardiovascular disease. © 2009 American Journal of Hypertension, Ltd.
- Description: C1
Systematic genetic analysis of fibroblast growth factor signalling pathway uncovers fibroblast growth factor binding protein 1 (FGFBP1) as a novel gene of essential hypertension
- Authors: Tomaszewski, Maciej , Charchar, Fadi , Barnes, Timothy , Maric, Christine , Samani, Nilesh , Zukowska-Szczechowska, Ewa
- Date: 2009
- Type: Text , Conference paper
- Relation: , p. S148
- Full Text: false
Whole genome survey of copy number variation between the spontaneously hypersensitive rat and the wistar-kyoto rat
- Authors: Charchar, Fadi , Dixon, Richard , Kaiser, Michael , Bingham, Andrew , Samani, Nilesh
- Date: 2009
- Type: Text , Journal article
- Relation: Hypertension Vol. 53, no. 6 (2009), p. 1103-1104
- Full Text: false
- Reviewed:
Y chromosome haplogroup as a novel biological risk factor for coronary artery disease - The results of tracking paternal lineages in the west of Scotland primary prevention study (WOSCOPS)
- Authors: Charchar, Fadi , Tomaszewski, Maciej , Barnes, Timothy , Wang, Y. , Brouilette, S. W. , Codd, Veryan , Bani-Mustafa, Ahmed , Padmanabhan, Sandosh , Dominiczak, Anna , Ford, I. , Samani, Nilesh
- Date: 2009
- Type: Text , Conference paper
- Relation: , p. S448-S448
- Full Text: false
FGF21 signalling pathway and metabolic traits - genetic association analysis
- Authors: Kaess, Bernhard , Barnes, Timothy , Stark, Klaus , Charchar, Fadi , Waterworth, Dawn , Song, Kijoung , Wang, William , Vollenweider, Peter , Waeber, Gerard , Mooser, Vincent , Zukowska-Szczechowska, Ewa , Samani, Nilesh , Hengstenberg, Christian , Tomaszewski, Maciej
- Date: 2010
- Type: Text , Journal article
- Relation: European Journal of Human Genetics Vol. 18, no. 12 (2010), p. 1344-1348
- Full Text: false
- Reviewed:
- Description: Fibroblast growth factor 21 (FGF21) is a novel master regulator of metabolic profile. The biological actions of FGF21 are elicited upon its klotho beta (KLB)-facilitated binding to FGF receptor 1 (FGFR1), FGFR2 and FGFR3. We hypothesised that common polymorphisms in the FGF21 signalling pathway may be associated with metabolic risk. At the screening stage, we examined associations between 63 common single-nucleotide polymorphisms (SNPs) in five genes of this pathway (FGF21, KLB, FGFR1, FGFR2, FGFR3) and four metabolic phenotypes (LDL cholesterol-LDL-C, HDL-cholesterol-HDL-C, triglycerides and body mass index) in 629 individuals from Silesian Hypertension Study (SHS). Replication analyses were performed in 5478 unrelated individuals of the Swiss CoLaus cohort (imputed genotypes) and in 3030 directly genotyped individuals of the German Myocardial Infarction Family Study (GerMIFS). Of 54 SNPs that met quality control criteria after genotyping in SHS, 4 (rs4733946 and rs7012413 in FGFR1; rs2071616 in FGFR2 and rs7670903 in KLB) showed suggestive association with LDL-C (P=0.0006, P=0.0013, P=0.0055, P=0.011, respectively) and 1 (rs2608819 in KLB) was associated with body mass index (P=0.011); all with false discovery rate q<0.5. Of these, only one FGFR2 polymorphism (rs2071616) showed replicated association with LDL-C in both CoLaus (P=0.009) and men from GerMIFS (P=0.017). The direction of allelic effect of rs2071616 upon LDL-C was consistent in all examined populations. These data show that common genetic variations in FGFR2 may be associated with LDL-C in subjects of white European ancestry
Fibroblast growth factor binding protein 1 gene (FGFBP1) and hypertension d from pathway analysis to renal glomerulus
- 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.
Genetic architecture of ambulatory blood pressure in the general population insights from cardiovascular gene-centric array
- Authors: Tomaszewski, Maciej , Debiec, Radoslaw , Braund, Peter , Nelson, Christopher , Hardwick, Robert , Christofidou, Paraskevi , Denniff, Matthew , Codd, Veryan , Rafelt, Suzanne , van der Harst, Pim , Waterworth, Dawn , Song, Kijoung , Vollenweider, Peter , Waeber, Gerard , Zukowska-Szczechowska, Ewa , Burton, Paul , Mooser, Vincent , Charchar, Fadi , Thompson, John , Tobin, Martin , Samani, Nilesh
- Date: 2010
- Type: Text , Journal article
- Relation: Hypertension Vol. 56, no. 6 (2010), p. 1069-U146
- Full Text: false
- Reviewed:
- Description: Genetic determinants of blood pressure are poorly defined. We undertook a large-scale, gene-centric analysis to identify loci and pathways associated with ambulatory systolic and diastolic blood pressure. We measured 24-hour ambulatory blood pressure in 2020 individuals from 520 white European nuclear families (the Genetic Regulation of Arterial Pressure of Humans in the Community Study) and genotyped their DNA using the Illumina HumanCVD BeadChip array, which contains approximate to 50 000 single nucleotide polymorphisms in >2000 cardiovascular candidate loci. We found a strong association between rs13306560 polymorphism in the promoter region of MTHFR and CLCN6 and mean 24-hour diastolic blood pressure; each minor allele copy of rs13306560 was associated with 2.6 mm Hg lower mean 24-hour diastolic blood pressure (P=1.2 x 10(-8)). rs13306560 was also associated with clinic diastolic blood pressure in a combined analysis of 8129 subjects from the Genetic Regulation of Arterial Pressure of Humans in the Community Study, the CoLaus Study, and the Silesian Cardiovascular Study (P=5.4 x 10(-6)). Additional analysis of associations between variants in gene ontology-defined pathways and mean 24-hour blood pressure in the Genetic Regulation of Arterial Pressure of Humans in the Community Study showed that cell survival control signaling cascades could play a role in blood pressure regulation. There was also a significant overrepresentation of rare variants (minor allele frequency: <0.05) among polymorphisms showing at least nominal association with mean 24-hour blood pressure indicating that a considerable proportion of its heritability may be explained by uncommon alleles. Through a large-scale gene-centric analysis of ambulatory blood pressure, we identified an association of a novel variant at the MTHFR/CLNC6 locus with diastolic blood pressure and provided new insights into the genetic architecture of blood pressure.
Whole genome survey of copy number variation in the spontaneously hypertensive rat relationship to quantitative trait loci, gene expression, and blood pressure
- Authors: Charchar, Fadi , Kaiser, Michael , Bingham, Andrew , Fotinatos, Nina , Ahmady, Fahima , Tomaszewski, Maciej , Samani, Nilesh
- Date: 2010
- Type: Text , Journal article
- Relation: Hypertension Vol. 55, no. 5 (2010), p. 1231-1238
- Full Text: false
- Reviewed:
- Description: Copy number variation has emerged recently as an important genetic mechanism leading to phenotypic heterogeneity. The aim of our study was to determine whether copy number variants (CNVs) exist between the spontaneously hypertensive rat (SHR) and its control strain, the Wistar-Kyoto rat, whether these map to quantitative trait loci in the rat and whether CNVs associate with gene expression or blood pressure differences between the 2 strains. We performed a comparative genomic hybridization assay between SHR and Wistar-Kyoto strains using a whole-genome array. In total, 16 CNVs were identified and validated (6 because of a relative loss of copy number in the SHR and 10 because of a relative gain). CNVs were present on rat autosomes 1, 3, 4, 6, 7, 10, 14, and 17 and varied in size from 10.0 kb to 1.6 Mb. Most of these CNVs mapped to chromosomal regions within previously identified quantitative trait loci, including those for blood pressure in the SHR. Transcriptomic experiment! s confirmed differences in the renal expression of several genes (including Ms4a6a, Ndr3, Egln1, Cd36, Sema3a, Ugt2b, and Idi21) located in some of the CNVs between STIR and Wistar-Kyoto rats. In F-2 animals derived from an SHRXWistar-Kyoto cross, we also found a significant increase in blood pressure associated with an increase in copy number in the Egln1 gene. Our findings suggest that, CNVs may play a role in the susceptibility to hypertension and related trails in the SHR. (Hypertension. 2010;55:1231-1238.)
Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study
- Authors: Fox, Ervin , Young, J. Hunter , Li, Yali , Dreisbach, Albert , Charchar, Fadi
- Date: 2011
- Type: Text , Journal article
- Relation: Human molecular genetics Vol. 20, no. 11 (June 2011), p. 2273
- Full Text:
- Reviewed:
- Description: The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.
Gene expression profiling reveals renin mRNA overexpression in human hypertensive kidneys and a role for microRNAs
- Authors: Marques, Francine , Campain, Anna , Tomaszewski, Maciej , Zukowska-Szczechowska, Ewa , Yang, Yee , Charchar, Fadi , Morris, Brian
- Date: 2011
- Type: Text , Journal article
- Relation: Hypertension Vol. 58, no. 6 (2011), p. 1093-1098
- Full Text: false
- Reviewed:
- Description: The kidney has long been invoked in the etiology of essential hypertension. This could involve alterations in expression of specific genes and microRNAs (miRNAs). The aim of the present study was to identify, at the transcriptome-wide level, mRNAs and miRNAs that were differentially expressed between kidneys of 15 untreated hypertensive and 7 normotensive white male subjects of white European ancestry. By microarray technology we found 14 genes and 11 miRNAs that were differentially expressed in the medulla. We then selected and confirmed by real-time quantitative PCR expression differences for NR4A1, NR4A2, NR4A3, PER1, and SIK1 mRNAs and for the miRNAs hsa-miR-638 and hsa-let-7c. Luciferase reporter gene experiments in human kidney (HEK293) cells confirmed the predicted binding of hsa-let-7c to the 3' untranslated region of NR4A2 mRNA. In the renal cortex we found differential expression of 46 genes and 13 miRNAs. We then confirmed expression differences for AIFM1, AMBP, APOE, CD36, EFNB1, NDUFAF1, PRDX5, REN, RENBP, SLC13A1, STX4, and TNNT2 mRNAs and for miRNAs hsa-miR-21, hsa-miR-126, hsa-miR-181a, hsa-miR-196a, hsa-miR-451, hsa-miR-638, and hsa-miR-663. Functional experiments in HEK293 cells demonstrated that hsa-miR-663 can bind to the REN and APOE 3' untranslated regions and can regulate REN and APOE mRNA levels, whereas hsa-miR-181a regulated REN and AIFM1 mRNA. Our data demonstrated for the first time that miRNAs can regulate renin expression. The observed downregulation of 2 miRNAs in hypertension could explain the elevation in intrarenal renin mRNA. Renin, CD36, and other mRNAs, as well as miRNAs and associated pathways identified in the present study, provide novel insights into hypertension etiology. © 2011 American Heart Association, Inc.