Genetic Polymorphisms in ABCA1 (rs2230806 and rs141420090) Gene and Their Association with the Risk of Type 2 Diabetes and Coronary Artery Disease: A Case-Control Study

Abstract

Background: CAD is linked to T2DM through common pathways in the metabolism and genome. The ATPbinding cassette transporter A1 (ABCA1) gene is a key component in cholesterol efflux, high-density lipoprotein (HDL) metabolism, and glucose-lipid balance. Genetic polymorphisms of ABCA1 could affect insulin sensitivity and lipid transport and consequently affect the susceptibility to both T2DM and CAD. Objective: To assess the relationship of ABCA1 polymorphisms: (rs2230806:R219K and rs141420090) with the risk of T2DM and CAD in north Indian population. Methods: The study comprised 600 unrelated cases (150 controls, 150 T2DM, 150 CAD, 150 T2DM+CAD). The PCR-RFLP technique was used for genotyping. The chi-square test was utilised to compare genotypic and allelic frequencies, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. All groups were found to be at Hardy-Weinberg equilibrium (HWE). Results: For rs2230806, the GG genotype frequency was significantly lower in T2DM patients (26%) compared to controls (37.3%) (χ²=6.39, p=0.041). The G allele frequency was significantly reduced in T2DM+CAD patients versus controls (49.7% vs 60.3%; OR=1.54, 95% CI: 1.22–2.13, p=0.014). Under the dominant model, the risk genotype (GA+AA) conferred significantly higher odds for T2DM (OR=1.98; p=0.012), CAD (OR=1.80; p=0.040), and T2DM+CAD (OR=2.62; p=0.002). However, in comparison, there was no significant association observed between rs141420090 and T2DM, CAD or T2DM+CAD in any genetic model (all p>0.05).Conclusion: ABCA1 rs2230806 is a potential genetic risk factor for T2DM and comorbid CAD in the Haryana population. rs141420090 does not appear to be associated with cardiometabolic disease susceptibility. The results need to be confirmed in larger multicenter studies