Genetic variants at the resistin gene promoter might have a role in atherogenesis in patients with coronary artery disease

Abstract

Introduction: Recent studies have demonstrated that resistin, an inflammatory adipokine, plays a key role in the pathogenesis of coronary artery disease (CAD). It is also known that the resistin gene (RETN) polymorphism, particularly in promoter region, is correlated with serum resistin levels and consequently an increased risk of CAD. This study investigates potential correlation between resistin gene polymorphism at -420C/G (rs1862513) and diabetes, as well as severity of CAD, in an Iranian cohort.
Methods: As a cross-sectional study, we recruited 113 subjects who were candidate for diagnostic coronary angiography. Laboratory measurements were FBS, OGTT, HbA1C, hsCRP, and lipid profile. Genotyping for Single Nucleotide Polymorphism (SNP) was performed using the PCR-RFLP method.
Results: Our findings showed that CAD patients with diabetes had significantly higher FBS, HbA₁C and cholesterol levels and more severe coronary artery stenosis compared to non-diabetic subjects. Besides, the frequencies of the RETN -420C/G genotype in the diabetic group were significantly higher as compared to those in non-diabetic group (P=0.009). Moreover, the CC genotype carriers had more than twofold increased risk of Type 2 diabetes mellitus (T2DM) compared with the GG carriers. Although, there was no statistically significant correlation between RETN -420C/G polymorphism and severity of CAD (P=0.3), when we reanalyzed data with entering both the patients with one and two involved coronary arteries as one group, it was observed that patients with CC genotype more severely suffered from the coronary artery disease than the other genotypes (P=0.04). The Odds Ratio (OR) and relative risk for CAD patients with CC genotype were 4.33 (95%CI=1.02-18.38) and 2.25 (95%CI=0.97-5.19, P= 0.04), respectively.
Conclusion: The results indicate that polymorphism in promoter region of RETN gene plays a role in the pathogenesis of coronary artery disease (probably due to its inflammatory characteristics) and the CC genotype is associated with an increased risk of diabetes and CAD compared to GG and CG.