Here we summarize the results of studies describing the associations between the UCP1 gene polymorphisms A-3826G, A-1766G, Met229Leu and Ala64Thr and polymorphism Trp64Arg in the β3-AR gene, their correlations and their associations with the occurrence of metabolic syndrome.
We investigated whether the -3826A/G polymorphism (rs1800592) of the uncoupling protein 1 gene (UCP1) and the rs4994" genes_norm="155">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.
Trp64Arg polymorphism of the ADRB3 gene may affect VF accumulation and be associated with MS, a cluster of conditions involving aggravated lipid metabolism and higher blood pressure, in Japanese children.
The non-synonymous rs4994 polymorphism of the ADRB3 gene was associated with T2D (Trp allele, OR = 0.62, p = 0.001) and MS (Trp allele, OR = 0.74, p = 0.018).
Comparison of populations indicated that no matter with the β3-AR gene mutation or not, the prevalence of MS in obese subjects was significantly higher than normal weight subjects (χ(2) = 28.240 and χ(2) = 15.586, all P < 0.005).
Multiple logistic regression analysis including smoking, sex, and age as confounding factors showed no interaction between MS and ADRB3 polymorphism (odds ratio: 0.94; 95% confidence interval: 0.59-1.49; p=0.78).
To determine whether this SNP affects insulin resistance syndrome associated with type 2 diabetes, we examined its effects on susceptibility to obesity, hyperlipidemia and hypertension in type 2 diabetic subjects and on susceptibility to type 2 diabetes by interaction with other frequent genes involved in lipid metabolism, namely, beta3-adrenergic receptor (b3AR) Trp64Arg, phosphodiesterase 3B (PDE3B) c.1389G>A or lysosomal acid lipase (LAL) Thr-6Pro.
The Trp64Argbeta3AR variant is associated in some, but not all, studies with an earlier onset of Type 2 diabetes mellitus and features of the insulin resistance syndrome.
We conclude that in obese women the beta 3-AR polymorphism may be used as a genetic marker for visceral fat obesity and the insulin resistance syndrome.
The Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is unlikely to be a major genetic predisposer to NIDDM or insulin resistance syndrome in subjects from eastern Finland.
We recently identified a mutation in the human beta 3-adrenergic receptor (beta 3AR) gene (codon 64 TGGTrp -> CGGArg; TRP64ARG) that associates with features of the insulin resistance syndrome and an earlier onset of noninsulin-dependent diabetes mellitus (NIDDM).
We conclude that the beta 3-adrenergic receptor locus does not play an important role in NIDDM susceptibility or in the insulin resistance syndrome among members of families with a strong predisposition to NIDDM.
A possible pathogenic mutation in the beta 3-adrenergic-receptor gene (Trp64Arg) has been reported to be associated with an earlier age of onset of non-insulin-dependent diabetes mellitus (NIDDM) and clinical features of the insulin resistance syndrome in Pima Indian, Finnish and French subjects.
In addition, since recent studies suggest the contribution of beta3 adrenergic receptor to the insulin resistance syndrome, the gene encoding beta3 adrenergic receptor (ADRB3) was also studied.