Association study of genetic variants at TTC32-WDR35 gene cluster with coronary artery disease in Chinese Han population.

Background: TTC32-WDR35 gene cluster has been genome-wide significantly associated with coronary artery disease (CAD). However, the common variants in this region contributing to CAD risk remain elusive.

Methods: We performed a case-control study enrolling 935 CAD cases and 935 age-sex-frequency-matched controls from unrelated southwest Chinese Han population. Five variants were determined by TaqMan assay.

Results: This study indicated that rs721932 CG genotype was associated with CAD risk (OR = 0.68, 95% CI: 0.54-0.86; P = .001). Stratified analysis showed that the risk associated with rs12617744 AA genotype was robust in male (OR = 0.62, 95% CI: 0.42-0.93, P = .02). The gene dosage of the risk allele at rs12617744 showed a significant association with left circumflex artery disease (P = .027) and the number of vascular lesions in patients (P = .034). Moreover, the gene dosage of rs721932 risk allele was associated with vascular lesion numbers (P = .048) and the progression of CAD (P = .028). Compared with carriers of major alleles, the AA genotype of rs12617744 and GG genotype of rs721932 were both associated with plasma HDL level (P = .009 and 0.004, respectively). Expression quantitative trait locus (eQTL) results showed significantly different TTC32 expression of subjects as a function of SNPs (rs2278528, rs7594214, and rs721932) genotype in the artery. Besides, FPRP analysis did support the strong links between polymorphisms and CAD risk.

Conclusions: SNP rs721932 at TTC32-WDR35 Gene Cluster was associated with CAD risk, and rs12617744 was associated with the risk of CAD among males. Both SNPs may contribute to the regulation of plasma HDL levels and possibly to the severity of CAD in Chinese Han population.