Nonsynonymous T280M gene variant of CX3CR1 in South Indian population is associated with reduced risk for vascular disease in patients with diabetes mellitus

Abstract

BaCKgRouNd: Vascular inflammation leading to coronary artery disease (CAD) is a major complication of type 2 diabetes mellitus (T2DM). The chemokine receptor CX3CR1 is a key regulator in vascular injuryrelated inflammation. oBjeCTIVe: The authors examined the T280M and V249I gene variants of the CX3CR1 gene in patients with T2DM, CAD and CAD associated with T2DM, to understand the effect of these polymorphisms on the disease phenotype. MeThodS: Whole blood samples were collected from 913 South Indian subjects comprising 160 patients with T2DM, 284 with T2DM and CAD, 198 with CAD and 271 healthy subjects. T280M and V249I variants of the CX3CR1 gene were genotyped in these study subjects using polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis and PCR-DNA sequencing. ReSulTS:Multivariate logistic regression analysis revealed that the frequencies of 280M and 249I alleles were higher in controls than in cases in both the CAD and T2DM groups. Adjusted odds of T280M according to logistic regression were significant in all disease groups compared withhealthy subjects. Both MM and II genotypes of T280M and V249I polymorphisms were found to have an atheroprotective role in CAD and T2DM. The association of these polymorphisms were then examined in patients with CAD who were also diagnosed with diabetes. The M allele of T280M polymorphism was associated with attenuated risk for CAD and T2DM. CoNCluSIoNS:The present study demonstrated a protective role of the T280M variant of CX3CR1 gene for vascular complication in patients with T2DM. This polymorphism may reduce the binding strength of the chemokine receptor, thus attenuating inflammation both in vascular wall and adipose tissue.