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. 2021 Feb;35(2):e23594.
doi: 10.1002/jcla.23594. Epub 2020 Oct 2.

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

Ying Xu  1 , Yang Zhuo  1 , Mengliang Ye  2 , Mengmeng Li  1 , Xiaojun Tang  1 , Li Zhou  1
Affiliations

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

Ying Xu et al. J Clin Lab Anal. 2021 Feb.

Abstract

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.

Keywords: coronary artery disease; expression quantitative trait locus; severity; single nucleotide polymorphism.

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Conflict of interest statement

The authors declare no relationships that could be construed as a conflict of interest.

Figures

FIGURE 1
FIGURE 1
Analysis of rs12617744 and coronary artery disease (CAD) severity. A, The proportion of CAD patients with left circumflex artery disease (LCX) as a function of genotype. B, Association between the frequencies of the rs12617744 risk allele and number of vascular lesions. LCX indicates left circumflex artery disease; 0VD, 0‐vessel disease; 1VD, 1‐vessel disease; 2VD, 2‐vessel disease; and 3VD, 3‐vessel disease
FIGURE 2
FIGURE 2
Analysis of rs721932 and coronary artery disease (CAD) severity. A, Association between the frequencies of the rs721932 minor allele and number of vascular lesions; B, Association between the frequencies of the rs721932 minor allele and the progress of CAD. SAP indicates stable angina pectoris; UAP, unstable angina pectoris; MI, myocardial infarction
FIGURE 3
FIGURE 3
Expression Quantitative Trait Loci (eQTL) analysis using data in Genotype‐Tissue Expression Project (GTEx) database. A, the TTC32 gene expression level as a function of rs2278528 genotype in coronary artery and aorta artert; B, the TTC32 gene expression level as a function of rs7594214 genotype in coronary arteryand aorta artert; C, the gene expression level of TTC32 as a function of rs721932 genotype in tibial artery
See this image and copyright information in PMC

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