Association study of genetic variants at TTC32-WDR35 gene cluster with coronary artery disease in Chinese Han population.
Association study of genetic variants at TTC32-WDR35 gene cluster with coronary artery disease in Chinese Han population.
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中国汉族人群TTC32-WDR35基因簇遗传变异与冠心病的关联研究
DOI：
10.1002/jcla.23594
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发表时间：
2021-03
影响因子：
2.7
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Xu Y;Zhuo Y;Ye M;Li M;Tang X;Zhou L
TTC 32 ‐ WDR 35基因簇在全基因组范围内与冠状动脉疾病（CAD）显著相关。然而，该地区导致CAD风险的常见变异仍然难以捉摸。我们进行了一项病例对照研究，纳入了935例CAD病例和935例年龄-性别-频率匹配的对照，这些病例和对照来自无关的中国西南部汉族人群。通过TaqMan测定确定五种变体。这项研究表明，rs721932 CG基因型与CAD风险相关（OR = 0.68，95% CI：0.54 - 0.86; P = 0.001）。分层分析显示，rs 12617744 AA基因型在男性中的风险稳健（OR = 0.62，95% CI：0.42 - 0.93，P = 0.02）。rs 12617744的危险等位基因的基因剂量与患者的左回旋支疾病（P = 0.027）和血管病变数量（P = 0.034）显著相关。此外，rs721932危险等位基因的基因剂量与血管病变数量（P = 0.048）和CAD进展（P = 0.028）相关。与主要等位基因携带者相比，rs 12617744的AA基因型和rs721932的GG基因型均与血浆HDL水平相关（P = 0.009和0.004）。表达数量性状位点（eQTL）结果显示，受试者的TTC 32表达随动脉中SNP（rs 2278528、rs7594214和rs721932）基因型的变化而显著不同。此外，FPRP分析确实支持多态性与CAD风险之间的密切联系。TTC 32-WDR 35基因簇的SNP rs721932与男性CAD风险相关，rs 12617744与男性CAD风险相关。这两个SNPs可能与中国汉族人群血浆HDL水平的调节有关，并可能与CAD的严重程度有关。TTC 32-WDR 35基因簇的SNP与CAD风险显著相关。这两个SNPs可能有助于调节血浆HDL水平，并可能在中国汉族人群中CAD的严重程度。
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. 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. 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. 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. SNPs at TTC32‐WDR35 Gene Cluster are significantly associated with CAD risk. Both SNPs may contribute to regulation of plasma HDL levels and possibly to the severity of CAD in a Chinese Han population.
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