Three Novel Genetic Variants in the FAM110D, CACNA1A, and NLRP12 Genes Are Associated With Susceptibility to Hypertension Among Dai People.

Abstract

Although the genetic factors associated with hypertension remain unknown, genetic variations in genes related to ion channels, inflammation, and the cell cycle may affect susceptibility to hypertension. In the present study, the association between hypertension and 10 candidate single-nucleotide polymorphisms (SNPs) was evaluated among Chinese Dai people, who have a smaller gene pool than Han individuals. A total of 1,193 samples from Dai people were collected, including 488 with hypertension and 705 with normal blood pressure. Based on the preliminary results of whole-genome sequencing among pools of individuals (Pool-seq), 10 candidate SNPs in 6 genes (FAM110D, ADD1, RAG1, CACNA1C, CACNA1A, and NLRP12) were genotyped in the case and control groups by multiplex PCR for SNP genotyping with next-generation sequencing (MultiPCR-NGS). The relationship between hypertension and each candidate SNP was evaluated using the χ 2 test and multiple logistic regression analysis. The χ 2 test showed that the allele frequencies of rs3748856 in FAM110D, rs139118504 in CACNA1A, and rs34436714 in NLRP12 were significantly different between the case and control groups (P < 0.005). After adjusting for age, body mass index, total cholesterol, triglyceride, and low-density lipoprotein, logistic regression analyses revealed that the association between the 3 SNPs and hypertension among Dai people remained significant (P = 0.012, 2.71 × 10-4, and 0.017, respectively). These findings indicate that there may be different molecular pathogeneses of hypertension among Dai people, which should be noted in future studies.