Susceptible gene polymorphism in patients with three-vessel coronary artery disease

Data of susceptible gene polymorphisms related to progression of coronary atherosclerosis in patients with three-vessel disease (TVD) is limited in China. This case-control study aimed to analyze the differences of variant carrier frequencies between cases and controls, and to explain the possible genetic effects on the progression of TVD.

A total of 8943 TVD patients were consecutively enrolled. Major adverse cardiac and cerebrovascular events (MACCE) included all-cause death, acute myocardial infarction, repeat revascularization, readmission and stroke. Patients with 1-year MACCE in this cohort were selected as MACCE group. Blood samples from MACCE group and non-CAD control groups were collected, and a deoxyribonucleic acid library was created. A total of 34 tag or hot single nucleotide polymorphisms (SNPs) in six genes including CDKN2B-AS1, ADAMTS7, ABO, ADAMTS13, IL-18, and PECAM1 were analyzed by a SNPscan™ multi-genotyping kit. Carrier frequencies of each SNP were compared between the two groups using dominant, recessive and codominant allele model, respectively. Multivariate logistic regression model was established.

Variant allele frequencies of rs10757274, rs1333042, rs1333049, rs4977574, rs9632884, rs1063192 and rs3217986 on CDKN2B-AS1 gene showed significant differences between the two groups in at least one allele model. Variant allele frequency of rs3217986 was not statistically significant after adjusting for the false discovery rate using Benjamini-Hochberg procedure (Q > 0.05). Variant allele frequencies of rs1333049, rs10757274, rs4977574 on CDKN2B-AS1 gene were significantly higher in MACCE group in all dominant, recessive and codominant models. Rs1055432 on ADAMTS13 and rs8176694 on ABO gene showed threshold significance between the two groups. After multivariable adjustment, G mutant homozygous rs9632884 (GG vs. GC + CC) (OR: 0.24; 95% CI: 0.09-0.65; P = 0.005) on CDKN2B-AS1 gene were independent protective factor of MACCE in recessive model.

In patients with TVD in China, variant alleles on CDKN2B-AS1 gene may form part of the genetic basis of coronary atherosclerosis progression, promoting or suppressing ischemic events.