The presence of at least three alleles of the ADRB3 Trp64Arg (C/T) and UCP1 -3826A/G polymorphisms is associated with protection to overweight/obesity and with higher high-density lipoprotein cholesterol levels in Caucasian-Brazilian patients with type 2 diabetes

We investigated whether the -3826A/G polymorphism (rs1800592) of the uncoupling protein 1 gene (UCP1) and the Trp64Arg polymorphism (rs4994) of the β3-adrenergic receptor gene (ADRB3) are associated with type 2 diabetes mellitus (T2DM) and features of metabolic syndrome in a Brazilian-Caucasian population. Both polymorphisms were genotyped in 1015 T2DM patients and 561 nondiabetic subjects. The combined effect of both polymorphisms on T2DM and metabolic syndrome-related parameters was analyzed according to a triallelic inheritance pattern, by which at least three minor alleles from two loci are necessary for trait manifestation. UCP1 -3826A/G and ADRB3 Trp64Arg polymorphisms were not associated with T2DM (P>0.05). Patients carrying the ADRB3 64Arg allele had higher fasting plasma glucose and high-density lipoprotein cholesterol (HDL-C) than patients with the Trp64Trp genotype (P=0.0001 and P=0.015, respectively). The 64Arg allele was also associated with protection against overweight/obesity (body mass index ≥ 25 kg/m(2); odds ratio [OR]=0.598; P=0.014). Interestingly, prevalence of overweight/obesity was lower among carriers of at least three minor alleles of the -3826A/G and ADRB3 Trp64Arg polymorphisms than among patients with fewer than three minor alleles (54.5% vs. 79.1%; OR=0.288; P=0.007, respectively). Subjects with at least three minor alleles also had higher HDL-C levels (P=0.018). UCP1 -3826A/G and ADRB3 Trp64Arg polymorphisms may have a combined effect in the modulation of overweight/obesity and HDL-C levels in type 2 diabetes mellitus (T2DM) Caucasian-Brazilian patients.