Associations of Variants in theCACNA1AandCACNA1CGenes With Longitudinal Blood Pressure Changes and Hypertension Incidence: The GenSalt Study

BACKGROUND: We aimed to examine the associations of voltage-dependent calcium-channel genes CACNA1A and CACNA1C with blood pressure (BP) changes and hypertension incidence in a longitudinal family study. METHODS: A total of 1,768 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were eligible for the current study. Nine BP measurements were obtained at baseline and each follow-up visit using a random-zero sphygmomanometer. Mixed-effect models were used to assess additive associations of 176 tag single-nucleotide polymorphisms (SNPs) in CACNA1A and CACNA1C with longitudinal BP changes and hypertension incidence. The truncated product method was used for gene-based analysis. The Bonferroni correction was used for adjustment of multiple testing. RESULTS: During an average of 7.2 years of follow-up, 512 (32.1%) participants developed hypertension. CACNA1A SNP rs8182538 was significantly associated with longitudinal diastolic BP (DBP) change after Bonferroni correction ( Pinteraction = 9.90×10 -5 ), with mean DBP increases of 0.85, 1.03, and 1.19mm Hg per year for participants with genotypes C/C , C/T , and T/T , respectively. A similar trend was observed for the association of rs8182538 with systolic BP (SBP) change. In the gene-based analysis, CACNA1A and CACNA1C were significantly associated with DBP change ( P = 2.0×10 -5 ) and SBP change ( P = 1.4×10 -4 ) after Bonferroni correction, respectively. The gene-based associations remained significant after removing rs8182538 within CACNA1A and rs758116 within CACNA1C in sensitivity analysis. CONCLUSIONS: Our findings indicated that CACNA1A and CACNA1C might contribute to BP changes over time in Han Chinese population. Further replication of these findings is warranted.