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Association of renin-angiotensin and endothelial nitric oxide synthase gene polymorphisms with blood pressure progression and incident hypertension: prospective cohort study.

ABSTRACT: The renin-angiotensin system and endothelial function have both been associated with hypertension. The aim of the present study was to assess the relationship of six previously characterized gene variants in the renin-angiotensin system and the NOS3 gene with blood pressure progression and incident hypertension.We analyzed data from 18 436 Caucasian women who participated in a prospective cohort study and were free of hypertension at baseline. Six previously characterized single nucleotide polymorphisms (NOS3 rs1800779, NOS3 rs3918226, NOS3 rs1799983, ACE rs1799752, AGT rs699, and AGTR1 rs5186) were genotyped. Blood pressure progression at 48 months and incident hypertension during the entire follow-up according to the different genotypes and inferred haplotypes were assessed by logistic regression and Cox proportional hazards models, respectively.At 48 months, 47.4% of the women had blood pressure progression. The odds ratios (95% confidence intervals) for blood pressure progression associated with NOS3 rs1800779, NOS3 rs3918226, NOS3 rs1799983, ACE rs1799752, AGT rs699, and AGTR1 rs5186 were 1.00 (0.96-1.05), 1.00 (0.92-1.09), 0.99 (0.94-1.04), 0.96 (0.92-1.01), 1.04 (0.99-1.08), and 1.03 (0.98-1.08), respectively. During 9.8 years of follow-up, 29.6% of women developed incident hypertension. The hazard ratios (95% confidence interval) for the six polymorphisms were 1.01 (0.97-1.06), 1.06 (0.99-1.14), 1.05 (1.01-1.09), 0.99 (0.95-1.02), 1.01 (0.97-1.05), and 0.99 (0.95-1.04). NOS3 haplotypes were not significantly associated with blood pressure progression (P = 0.91) or incident hypertension (P = 0.10).Blood pressure progression and incident hypertension are not consistently associated with six well-characterized genetic polymorphisms of the renin-angiotensin system and the NOS3 gene in a large cohort of Caucasian women.

SUBMITTER: Conen D

PROVIDER: S-EPMC2654571 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Association of renin-angiotensin and endothelial nitric oxide synthase gene polymorphisms with blood pressure progression and incident hypertension: prospective cohort study.

Conen David D Glynn Robert J RJ Buring Julie E JE Ridker Paul M PM Zee Robert Y L RY

Journal of hypertension 20080901 9

<h4>Objective</h4>The renin-angiotensin system and endothelial function have both been associated with hypertension. The aim of the present study was to assess the relationship of six previously characterized gene variants in the renin-angiotensin system and the NOS3 gene with blood pressure progression and incident hypertension.<h4>Methods</h4>We analyzed data from 18 436 Caucasian women who participated in a prospective cohort study and were free of hypertension at baseline. Six previously cha ...[more]

PMID: 18698212

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Project description:BackgroundNumerous individually underpowered association studies have been conducted on endothelial nitric oxide synthase (eNOS) genetic variants across different ethnic populations, however, the results are often irreproducible. We therefore aimed to meta-analyze three eNOS widely-evaluated polymorphisms, G894T (rs1799983) in exon 7, 4b/a in intron 4, and T-786C (rs2070744) in promoter region, in association with hypertension from both English and Chinese publications, while addressing between-study heterogeneity and publication bias.MethodsData were analyzed using Stata software (version 11.0), and random-effects model was applied irrespective of between-study heterogeneity, which was evaluated by subgroup and meta-regression analyses. Publication bias was weighed using the Egger's test and funnel plot.ResultsThere were total 19284/26003 cases/controls for G894T, and 6890/6858 for 4b/a, and 5346/6392 for T-786C polymorphism. Overall comparison of allele 894T with 894G in all study populations yielded a 16% increased risk for hypertension (odds ratio [OR] = 1.16; 95% confidence interval [95% CI]: 1.07-1.27; P = 0.001), and particularly a 32% increased risk (95% CI: 1.16-1.52; P<0.0005) in Asians and a 40% increased risk (95% CI: 1.19-1.65; P<0.0005) in Chinese. Further subgroup analyses suggested that published languages accounted for the heterogeneity for G894T polymorphism. The overall OR of allele 4a versus 4b was 1.29 (95% CI: 1.13-1.46; P<0.0005) in all study populations, and this estimate was potentiated in Asians (OR = 1.42; 95% CI: 1.16-1.72; P<0.0005). For T-786C, ethnicity-stratified analyses suggested a significantly increased risk for -786C allele (OR = 1.25; 95% CI: 1.06-1.47; P = 0.007) and -786CC genotype (OR = 1.69; 95% CI: 1.20-2.38; P = 0.003) in Whites. As an aside, the aforementioned risk estimates reached significance after Bonferroni correction. Finally, meta-regression analysis on other study-level covariates failed to provide any significance for all polymorphisms.ConclusionWe, via a comprehensive meta-analysis, ascertained the role of eNOS G894T and 4b/a polymorphisms on hypertension in Asians, and T-786C polymorphism in Whites.

Dataset Information

Association of renin-angiotensin and endothelial nitric oxide synthase gene polymorphisms with blood pressure progression and incident hypertension: prospective cohort study.

Publications

Association of renin-angiotensin and endothelial nitric oxide synthase gene polymorphisms with blood pressure progression and incident hypertension: prospective cohort study.

Similar Datasets

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