Dataset Information

Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.

ABSTRACT: OBJECTIVE:Genetic risk factors for essential hypertension are largely unknown. The aim of the present study was to assess the association of 77 previously characterized gene variants in 52 candidate genes from various biological pathways with blood pressure (BP) progression and incident hypertension. METHODS:We analyzed data from 18 738 white women who participated in a prospective cohort study and were free of hypertension at baseline. BP progression at 48 months and incident hypertension during the entire follow-up according to the different genotypes were assessed by logistic regression and Cox proportional-hazards models, respectively. RESULTS:At 48 months of follow-up, 7889 of 16 635 women (47.4%) had BP progression. Only three of 70 polymorphisms with a minor allele frequency of at least 2% had a significant association with BP progression. The odds ratio [95% confidence interval (CI)] for 5,10-methylenetetrahydrofolate reductase (MTHFR) rs1801133 (minor allele T), natriuretic peptide precursor A (NPPA) rs5063 (minor allele A) and NPPA rs5065 (minor allele C) were 1.05 (1.00-1.10), 0.84 (0.76-0.94) and 0.93 (0.88-1.00), respectively. After adjustment for multiple testing using the false discovery rate, only the NPPA rs5063 association remained significant. During a median follow-up of 9.8 years, 5540 of 18 738 women developed incident hypertension. Only five of 70 polymorphisms were significantly associated with incident hypertension. The hazard ratio (95% CI) for interleukin 6 (IL-6) rs1800795 (minor allele C), MTHFR rs1801133, NPPA rs5063, nitric oxide synthase 3 rs1799983 (minor allele T) and transforming growth factor, beta 1 rs1800469 (minor allele T) were 0.96 (0.92-1.00), 1.06 (1.02-1.10), 0.88 (0.80-0.96), 1.05 (1.01-1.09) and 1.05 (1.01-1.10), respectively. After adjustment for multiple testing, none of these associations remained significant. CONCLUSION:NPPA gene polymorphisms may have a role in BP progression and incident hypertension. Our data also provide moderate confirmatory evidence of association between MTHFR rs1801133 and the development of hypertension.

SUBMITTER: Conen D

PROVIDER: S-EPMC2663916 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.

Conen David D Cheng Suzanne S Steiner Lori L LL Buring Julie E JE Ridker Paul M PM Zee Robert Y L RY

Journal of hypertension 20090301 3

<h4>Objective</h4>Genetic risk factors for essential hypertension are largely unknown. The aim of the present study was to assess the association of 77 previously characterized gene variants in 52 candidate genes from various biological pathways with blood pressure (BP) progression and incident hypertension.<h4>Methods</h4>We analyzed data from 18 738 white women who participated in a prospective cohort study and were free of hypertension at baseline. BP progression at 48 months and incident hyp ...[more]

PMID: 19330901

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Project description:Background Genome-wide association studies have identified >1000 genetic variants cross-sectionally associated with blood pressure variation and prevalent hypertension. These discoveries might aid the early identification of subpopulations at risk of developing hypertension or provide targets for drug development, amongst other applications. The aim of the present study was to analyze the association of blood pressure-associated variants with long-term changes (10 years) in blood pressure and also to assess their ability to predict hypertension incidence compared with traditional risk variables in a Swedish population. Methods and Results We constructed 6 genetic risk scores (GRSs) by summing the dosage of the effect allele at each locus of genetic variants previously associated with blood pressure traits (systolic blood pressure GRS (GRSSBP): 554 variants; diastolic blood pressure GRS (GRSDBP): 481 variants; mean arterial pressure GRS (GRSMAP): 20 variants; pulse pressure GRS (GRSPP): 478 variants; hypertension GRS (GRSHTN): 22 variants; combined GRS (GRScomb): 1152 variants). Each GRS was longitudinally associated with its corresponding blood pressure trait, with estimated effects per GRS SD unit of 0.50 to 1.21 mm Hg for quantitative traits and odds ratios (ORs) of 1.10 to 1.35 for hypertension incidence traits. The GRScomb was also significantly associated with hypertension incidence defined according to European guidelines (OR, 1.22 per SD; 95% CI, 1.10‒1.35) but not US guidelines (OR, 1.11 per SD; 95% CI, 0.99‒1.25) while controlling for traditional risk factors. The addition of GRScomb to a model containing traditional risk factors only marginally improved discrimination (Δarea under the ROC curve = 0.001-0.002). Conclusions GRSs based on discovered blood pressure-associated variants are associated with long-term changes in blood pressure traits and hypertension incidence, but the inclusion of genetic factors in a model composed of conventional hypertension risk factors did not yield a material increase in predictive ability.

Project description:BACKGROUND:Long-term exposure to particulate matter (PM) air pollution may increase blood pressure and the risk of hypertension. However, epidemiological evidence is scarce and inconsistent. OBJECTIVES:We investigated the associations between long-term exposure to PM with an aerodynamic diameter <2.5?m (PM2.5), blood pressure, and incident hypertension in a large Taiwanese cohort. METHODS:We studied 361,560 adults ?18y old from a large cohort who participated in a standard medical examination program during 2001 to 2014. Among this group, 125,913 nonhypertensive participants were followed up. A satellite-based spatiotemporal model was used to estimate the 2-y average PM2.5 concentrations at each participant's address. Multivariable linear regression was used in the cross-sectional data analysis with the 361,560 participants to investigate the associations between PM2.5 and systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP), and Cox proportional hazard regression was used in the cohort data analysis with the 125,913 participants to investigate the associations between PM2.5 and incident hypertension. RESULTS:Each 10-?g/m3 increment in the 2-y average PM2.5 concentration was associated with increases of 0.45?mmHg [95% confidence interval (CI): 0.40, 0.50], 0.07?mmHg (95% CI: 0.04, 0.11), and 0.38?mmHg (95% CI: 0.33, 0.42) in SBP, DBP, and PP, respectively, after adjusting for a wide range of covariates and possible confounders. Each 10-?g/m3 increment in the 2-y average PM2.5 concentration was associated with an increase of 3% in the risk of developing hypertension [hazard?ratio=1.03 (95% CI: 1.01, 1.05)]. Stratified and sensitivity analyses yielded similar results. CONCLUSIONS:Long-term exposure to PM2.5 air pollution is associated with higher blood pressure and an increased risk of hypertension. These findings reinforce the importance of air pollution mitigation strategies to reduce the risk of cardiovascular disease. https://doi.org/10.1289/EHP2466.

Dataset Information

Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.

Publications

Association of 77 polymorphisms in 52 candidate genes with blood pressure progression and incident hypertension: the Women's Genome Health Study.

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