Involvement of beta-3-Adrenergic Gene Polymorphism in Insulin Resistance in Iraqi Type 2 Diabetic Patients

Abstract

A tryptophan to arginine substitution (TGG?CGG) in codon 64 (Trp 64 Arg) of ?3-adrenergic receptor is thought to be important for binding of noradrenaline and G proteins with ?3-adrenergic receptor in adipose cells. ?3-adrenergic receptor polymorphism may lead to a decrease in thermogenesis and lipolysis in adipose tissue. Therefore, an impairment of ?3-adrenergic receptor function may lead to obesity and insulin resistance. The present study was designed to estimate prevalence and association of ?3-adrenergic receptor gene T?C (Trp 64 Arg) SNP in insulin resistance type 2 diabetic patients in Iraq. To achieve this aim, 103 of type 2 diabetic patients and 57 apparently healthy control group were subjected to the study. The results of present study show that the heterozygous genotype (TC) of  ?3-adrenergic receptor gene T?C (Trp 64 Arg) SNP was significantly increased (OR=4.12, CI 95% 1.14-15.86, P < 0.05) the risk of type 2 diabetes mellitus four folds with respect to those of the wild genotype (TT). Also, the results revealed that significant increase (P < 0.05) in fasting insulin, HOMA, BMI and significant decrease (P < 0.05) in HDL-cholesterol of heterozygous genotype (TC) when compared with wild genotype (TT). Also, there are no significant differences in other clinical characteristics between wild genotype (TT) and heterozygous genotype (TC). The study concluded that ?3-adrenergic receptor gene T?C (Trp 64 Arg) SNP are associated and involved in the pathogenesis of insulin resistant type 2 diabetes mellitus.

Keyword: Diabetes Mellitus, Insulin resistance, Obesity, ?3-adrenergic receptor,  Trp 64 Arg