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Effects of IL-32 polymorphisms and IL-32 levels on the susceptibility and severity of coronary artery disease.

ABSTRACT:

Background

Interleukin-32 (IL-32) has long been proposed as a biomarker for coronary artery disease (CAD). We aimed to evaluate the association between IL-32 levels and coronary stenosis severity, IL-32 polymorphisms rs28372698 and rs4786370, and CAD susceptibility.

Methods

A total of 362 patients with definite or suspected CAD that underwent angiography were recruited (CAD group, n = 175; nonobstructive CAD group, n = 56; control group, n = 131). The severity of coronary stenosis was assessed using the Gensini score and the number of diseased vessels. IL-32 levels were determined using enzyme-linked immunosorbent assay. Gene polymorphisms were genotyped using PCR and sequencing techniques.

Results

IL-32 levels were significantly different at different levels of coronary artery stenosis (p < 0.05), and logIL-32 was positively correlated with the Gensini score (r = 0.357, p < 0.01). Multivariate logistic regression analysis revealed that IL-32 was independently associated with CAD (OR = 6.526, 95% CI: 3.344-12.739, p < 0.01). The receiver operating characteristic analysis revealed the area under the curve for discriminating the CAD and Gensini score were 0.605 and 0.613, respectively. Furthermore, IL-32 levels were significantly higher before percutaneous coronary intervention (PCI) than at 7 days post-PCI (p = 0.012). The homozygous TT genotype and T allele of rs28372698 were found to be associated with increased risk of CAD, while TT homozygosity and the T allele of rs4786370 with reduced risk of CAD (p < 0.05). However, both SNPs had no obvious effect on IL-32 levels or coronary stenosis severity in patients with CAD.

Conclusion

To the best of our knowledge, our study is the first to show that rs28372698 and rs4786370 are associated with CAD susceptibility in Chinese Han population. We also suggest that plasma IL-32 levels may be indicative of coronary artery stenosis and the efficacy of PCI and provide guidance for risk stratification and disease management.

SUBMITTER: Jin S

PROVIDER: S-EPMC8761453 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCase-control Genome-Wide Association Studies (GWAS) have identified single nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). The locus does not contain a clear candidate gene. Hence, the results of GWAS have raised an intense interest in delineating the basis for the observed association. We analyzed association of 4 SNPs at the 9p21 locus with the severity and progression of coronary atherosclerosis, as determined by serial quantitative coronary angiograms (QCA) in the well-characterized Lipoprotein Coronary Atherosclerosis Study (LCAS) population. The LCAS is a randomized placebo-control longitudinal follow-up study in patients with CAD conducted to test the effects of fluvastatin on progression or regression of coronary atherosclerosis.MethodsExtensive plasma lipid levels were measured at the baseline and 2 1/2 years after randomization. Likewise serial QCA was performed at the baseline and upon completion of the study. We genotyped the population for 4 SNPs, previously identified as the susceptibility SNPs for CAD in GWAS, using fluorogenic 5' nuclease assays. We reconstructed the haplotypes using Phase 2, analyzed SNP and haplotype effects using the Thesias software as well as by the conventional statistical methods.ResultsOnly Caucasians were included since they comprised 90% of the study population (332/371 with available DNA sample). The 4 SNPs at the 9p21 locus were in tight linkage disequilibrium, leading to 3 common haplotypes in the LCAS population. We found no significant association between quantitative indices of severity of coronary atherosclerosis, such as minimal lumen diameter and number of coronary lesions or occlusions and the 9p21 SNPs and haplotypes. Likewise, there was no association between quantitative indices of progression of coronary atherosclerosis and the SNPs or haplotypes. Similarly, we found no significant SNP or haplotype effect on severity and progression of coronary atherosclerosis.ConclusionWe conclude the 4 SNPs at the 9p21 locus analyzed in this study do not impart major effects on the severity or progression of coronary atherosclerosis. The effect size may be very modest or the observed association of the CAD with SNPs at the 9p21 locus in the case-control GWAS reflect involvement of vascular mechanisms not directly related to the severity or progression of coronary atherosclerosis.