Association of polymorphism in both tryptophan 64 arginine of the beta 3-adrenergic receptor gene and TNF-alpha gene with features of the metabolic syndrome in Egyptians

ABSTRACT

Several candidate genes have been tested for their association with the metabolic syndrome. Among these genes, the Beta 3-Adrenergic receptor gene [ADRB3] and the TNF-alpha gene locus has been the object of many studies. Therefore the aim of this work was to investigate the possible association of the beta 3-Adrenergic Receptor Trp64Arg polymorphism and the -308G/A polymorphism in the promoter region of TNF-alpha, in a group of male Egyptians with features of the metabolic syndrome.30 male patients with features of metabolic syndrome [group I], fifteen age matched healthy males were included as controls [group II]. Patients and controls were subjected to full history taking, clinical examination stressing on blood pressure, waist circumference, and waist/ hip [W/H] ratio; laboratory investigations included lipid profile [TG, total cholesterol, HDL-C, LDL-C], FBS, fasting insulin and HOMA-IR index, and molecular detection of Trp64Arg variant of the beta 3- adrenergic receptor as well as the TNF alpha gene promoter polymoprhism using RFLP-PCR in blood. The studied clinical parameters, lipid profile, fasting blood sugar, fasting insulin and HOMA-IR index were significantly higher in group I than that observed in group II. There was no statistically significant difference between the beta 3- adrenergic receptor wild and mutant subjects among group I as regards the studied clinical parameters, lipid profile, fasting blood glucose, fasting serum insulin and HOMA-IR index. While subjects harboring the A allele of the TNF alpha gene promoter showed significant higher levels of fasting insulin [p=0.002] fasting blood glucose, [p=0.014] and HOMA index [p < 0.001] as well as a significant decrease in HDL cholesterol levels [p=0.041]. In contrast, no association was found with total cholesterol, LDL cholesterol, triglycerides levels between the different genotypes. The correlation between HOMA-IR index and other studied parameters was not statistically significant among group I. The beta-3-adrenergic receptor locus does not play an important role in the metabolic syndrome susceptibility or in the insulin resistance. While, the -308 G/A TNF-alpha gene variant might confer an increased risk for the development of insulin resistance