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 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. Blood pressure 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.
At 48 months of follow-up, 7889 of 16635 women (47.4%) had blood pressure progression. Only three 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 (minor allele T), 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 18738 women developed incident hypertension. Only five of 70 polymorphisms were significantly associated with incident hypertension. The hazard ratio (95% CI) for IL6 rs1800795 (minor allele C), MTHFR rs1801133, NPPA rs5063, NOS3 rs1799983 (minor allele T) and TGFB1 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.
NPPA gene polymorphisms may have a role in blood pressure progression and incident hypertension. Our data also provide moderate confirmatory evidence of association between MTHFR rs1801133 and hypertension.
Keywords: Blood pressure, Hypertension, Gene polymorphism, Natriuretic peptide precursor A, Methylenetetrahydrofolate Reductase