Associations of Renin-Angiotensin-Aldosterone System Genes With Blood Pressure Changes and Hypertension Incidence

BACKGROUND The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure (BP) regulation. The current study uses single-marker and gene-based analyses to examine the association between RAAS genes and longitudinal BP phenotypes in a Han Chinese population. METHODS A total of 1,768 participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were included in the current study. Twenty-seven BP measurements were taken using random-zero sphygmomanometers at baseline and 2 follow-up visits. Mixed-effect models were used to assess the additive associations of 106 single-nucleotide polymorphisms (SNPs) in 10 RAAS genes with longitudinal BP changes and hypertension incidence. Gene-based analyses were conducted using the truncated product method. Attempts were made to replicate significant findings among Asian participants of the Multi-ethnic Study of Atherosclerosis (MESA). False discovery rate procedures were used to adjust for multiple testing. RESULTS During an average of 7.2 years of follow-up, average systolic and diastolic BP increased, and 32.1% (512) of participants free from hypertension at baseline developed hypertension. NR3C2 SNPs rs7694064 and rs6856803 were significantly associated with longitudinal changes in systolic BP (P-interaction = 6.9 x 10(-5) and 8.2 x 10(-4), respectively). Through gene-based analysis, NR3C2 was found to be significantly associated with longitudinal systolic BP change (P value of 1.00 x 10(-7)), even after removal of significant markers rs7694064 and rs6856803 from the analysis. The association between NR3C2 and longitudinal systolic BP change was replicated in Asian MESA participants (P value of 1.00 x 10(-4)). CONCLUSIONS These findings indicate that NR3C2 may play an important role in BP progression and development of hypertension.