Association of β3-adrenergic receptor rs4994 polymorphisms with the risk of type 2 diabetes: A systematic review and meta-analysis.

AIM: The association of ADRB3 polymorphism with the risk of T2DM remains unclear perhaps due to different ethnicities and small study sizes. We systemically evaluated the association of β3-adrenergic receptor(ADRB3)rs4994 and type 2 diabetes(T2DM) by pooling all of the case-control studies reported, and also elucidated the association according to the ethnicity and obesity of the subjects.

METHODS: A literature search was conducted using PubMed, EMBASE, Cochrane Library, Korean scientific database, Chinese medical databases, and the Indian medical database to identify eligible studies for determining the association of ADRB3 rs4994 and T2DM risk. The association was examined in five genetic models: the allelic(AG), recessive(RG), dominant(DG), homozygous(HMG), and heterozygous(HTG) genetic models. Subgroup analyses stratified by ethnicity(Asians and others) were assessed.

RESULTS: This meta-analysis included 17 eligible studies meeting Hardy-Weinberg equilibrium consisting of 4864 patients with T2DM(cases) and 8779 people without diabetes(controls). All models had no heterogeneity or publication bias in the meta-analysis including all subjects. ADRB3 rs4994 polymorphism of all subjects was significantly associated with an increased risk of T2DM in all genetic models with random effects: AG(OR=1.18, 95% CI: 1.05-1.32), RG(OR=1.76, 95% CI: 1.27-2.42), DG(OR=1.16, 95% CI: 1.03-1.30), HMG (OR=1.78, 95% CI: 1.25-2.52), and HTG(OR=1.11, 95% CI: 1.01-1.23). Furthermore, in sub-group analysis all models except HTG exhibited significant associations between T2DM and ADRB3 in Asians. However, the non-Asian group had no significant association in any genetic models with random effects.

CONCLUSIONS: Middle-age adult Asians with the ADRB3 rs4994 minor alleles are at increased risk of T2DM.