Abstract 3135: Association of 77 Polymorphisms in 52 Candidate Genes with Blood Pressure Progression and Incident Hypertension: The Women’s Genome Health Study
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. We analyzed data from 18738 Caucasian 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. Adjustment for multiple testing was performed using the false discovery rate (FDR), and an FDR<0.20 was considered to indicate statistical significance. At 48 months of follow-up, 7890 of 16638 women (47.4%) had BP progression. Only 3 of 70 polymorphisms with a minor allele frequency >=2% had a significant association with blood pressure progression. The odds ratio (95% confidence interval (CI)) for MTHFR rs1801133, NPPA rs5063 and NPPA rs5065 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 FDR, only the NPPA rs5063 association with BP progression remained significant (FDR=0.10). During a median follow-up of 9.8 years, 5540 of 18738 women developed incident hypertension. Only 5 of 70 polymorphisms were significantly associated with incident hypertension. The hazard ratio (95% CI) for IL6 rs1800795, MTHFR rs1801133, NPPA rs5063, NOS3 rs1799983 and TGFB1 rs1800469 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. The associations of MTHFR rs1801133 and NPPA rs5063 with incident hypertension were of borderline significance after adjustment for multiple testing (FDR=0.22 for both comparisons). NPPA gene polymorphisms may have a role in BP progression and incident hypertension. Because an association between MTHFR rs1801133 and hypertension has been suggested in prior studies, our data also provide some confirmatory evidence for a potential implication of this genetic variant in the pathogenesis of hypertension.