Unraveling the understudied influence of a lead variant in the 9p21 locus on the atherogenic index among type 2 diabetes patients with coronary artery disease.

Abstract

Introduction: The region on chromosome 9p21 has consistently been identified in genome-wide association studies (GWAS) as the top locus for type 2 diabetes (T2D), however, genetic variations in this locus affecting both T2D and coronary artery disease (CAD) require further characterized. Our aim was to assess the effects of rs10811661, a variant validated in GWAS, on log (TG/HDL-C), which has been associated with an atherogenic lipid profile.

Methods: A total of 121 patients with T2D who underwent coronary angiographic examination were included in this study. The patients were categorized into two groups, those with angiographically normal coronary arteries or less than 50% stenosis (non-CAD) and those having at least 70% stenosis in one of the main coronary arteries (severe CAD). The rs10811661 variant was genotyped using the restricted fragment length polymorphism (RFLP) analysis after PCR amplification.

Results: When the data was divided into tertiles according to HbA1c, our findings revealed that in tertile 3 (HbA1c ≥ 7.8%), the frequency of TT genotypes was higher compared to CT + CC genotypes (37.1% vs. 27.8%). T2D patients with CAD who carried the TT genotype had higher concentrations of log (TG/HDL) (p = 0.037) and TG (p = 0.003) compared to those with the C allele (CC or CT genotypes). After adjustment for covariates, the T allele of rs10811661 indicated significant associations with TG (OR = 1.66, 95% CI: 1.22-2.33, p = 0.002) and log (TG/HDL-C) (OR = 1.12, 95% CI: 1.02-2.13, p = 0.023) levels.

Conclusion: Our findings provide insight into how a GWAS-validated variant, rs10811661, can influence atherogenicity in patients with T2D and establish a link between this functional variant in the 9p21 locus and lipid factors associated with atherosclerosis. Further investigations are needed to understand the mechanisms by which this important variant influences lipid and lipoprotein levels, which could be useful in developing personalized medicine interventions.