Association between rs1042714 (Gln27Glu) gene polymorphism and obesity risk under dominant model.

<p>(Gln/Glu + Glu/Glu vs. Gln/Gln: OR: 1.2, 95% CI: 1.00–1.44, <i>I</i>² = 55%, P = 0.04).</p

Funnel plot for rs1042714 (Gln27Glu) gene polymorphism on heterozygote Gln/Glu vs.

<p>Gln/Gln. The funnel plot showed no apparent evidence of publication bias.</p

Association of Gln27Glu and Arg16Gly Polymorphisms in Beta2-Adrenergic Receptor Gene with Obesity Susceptibility: A Meta-Analysis

<div><p>Background</p><p>The beta2-adrenergic receptor (ADRB2) gene polymorphism has been implicated in susceptibility to obesity, but study results are still controversial.</p><p>Objective</p><p>The present meta-analysis is performed to determine whether there are any associations between the Gln27Glu (rs1042714) or the Arg16Gly (rs1042713) polymorphisms in ADRB2 and obesity susceptibility.</p><p>Methods</p><p>The PubMed (1950–2014), Embase (1974–2014), and China National Knowledge Infrastructure (CNKI, 1994–2014) databases were searched using the search terms (“Beta2-adrenergic receptor”, “β2-adrenergic receptor” or “ADRB2”), “polymorphism,” and “obesity”. Fixed- or random-effects pooled measures were determined on the bias of heterogeneity tests across studies. Publication bias was examined by Egger's test and the modified Begg's test.</p><p>Results</p><p>Eighteen published articles were selected for meta-analysis. Overall analyses showed that rs1042714 (Gln27Glu) was associated with significantly increased obesity risk in the heterozygote model (Gln/Glu vs. Gln/Gln: OR: 1.16, 95% CI: 1.04–1.30, <i>I</i>² = 49%, P = 0.009) and the dominant model (Gln/Glu + Glu/Glu vs. Gln/Gln: OR: 1.2, 95% CI: 1.00–1.44, <i>I</i>² = 55%, P = 0.04), whereas no significant association was found in the other models for rs1042714. Also, no significant association was found between the rs1042713 (Arg16Gly) gene polymorphism and the risk of obesity in all genetic models. In addition, neither rs1042713 (Arg16Gly) nor rs1042714 (Gln27Glu) showed any significant association with obesity susceptibility when the population were stratified based on gender.</p><p>Conclusion</p><p>Our meta-analysis revealed that the rs1042714 (Gln27Glu) polymorphism is associated with obesity susceptibility. However, our results do not support an association between rs1042713 (Arg16Gly) polymorphisms and obesity in the populations investigated. This conclusion warrants confirmation by more case-control and cohort studies.</p></div

Flow diagram of articles selection process for ADRB2 gene polymorphism and obesity risk.

<p>Flow diagram of articles selection process for ADRB2 gene polymorphism and obesity risk.</p

Distributions of ADRB2 Gln27/Glu and Arg16/Gly genotypes of eligible studies included in the meta-analysis.

<p>ADRB2, Beta 2-adrenergic receptor gene; Gln27Glu (rs1042714), at codon 27; Arg16Gly (rs1042713), at codon 16.</p

Methodological quality of 18 articles enrolled in our study by the “Newcastle-Ottawa Quality Assessment Scale”.

<p>Methodological quality of 18 articles enrolled in our study by the “Newcastle-Ottawa Quality Assessment Scale”.</p

Meta-analysis of rs1042714 (Gln27Glu) polymorphism on risk of obesity.

<p>Abbreviations: OR, odds ratio; CI, confidence interval; <i>I</i>², Cochran's c–based Q-statistic test for assessing the heterogeneity (>50% indicates a substantial heterogeneity).</p

Association between rs1042714 (Gln27Glu) gene polymorphism and obesity risk under heterozygote model.

<p>(Gln/Glu vs. Gln/Gln: OR: 1.16, 95% CI: 1.04–1.30, <i>I</i>² = 49%, P = 0.009).</p

Characteristics of studies ofADRB2 polymorphisms between obese people and controls included in the meta-analysis.

<p>Abbreviations: BMI, body mass index; ADRB2, Beta 2-adrenergic receptor gene; Gln27Glu (rs1042714), at codon 27; Arg16Gly (rs1042713), at codon 16.</p

TRO normalizes Pdx1 and Mafa protein levels.

<p>(A) INS-1 cells were transfected with the PPRE-luc plasmid for 24 h and then treated with NG or 10% GS for an additional 16 h before analysis in a dual-luciferase reporter assay. The firefly luciferase activity representing PPARγ activity was normalized to the <i>Renilla</i> activity of pRL-SV40. **<i>P</i><0.01 vs. NG + DMSO; ^{# #}<i>P</i><0.01 vs. GS + DMSO. (B) After co-transfection with PPRE-luc and PPARγor vector for 24 h, INS-1 cells were treated with NG or 10% GS for another 16 h. Cells extracts were analyzed using the dual-luciferase reporter assay. *<i>P</i><0.05 or **<i>P</i><0.01 vs. NG + vector + DMSO; ^#<i>P</i><0.05 or ^{# #}<i>P</i><0.01 vs. NG. (C) INS-1 cells were pre-treated with DMSO or 20 µmol/l TRO for 1 h and then exposed to NG or 5% GS for 16 h before detection of Pdx1 and Mafa levels by Western blot. β-Tubulin was used as an internal standard. (D) After transfection with the PPARγ over-expression plasmid for 24 h, INS-1 cells were treated with NG or 5% GS for an additional 16 h before harvesting for Western blot analysis of Pdx1 and Mafa levels. (E, F) INS-1 cells were pre-cultured with 20 µmol/l TRO for 1 h and then co-cultured with NG and 5% GS for the indicated time before analysis of <i>Pdx1</i> (E) and <i>Mafa</i> (F) mRNA levels by real-time RT-PCR. <i>β-Actin</i> was used as an internal standard. Values are the mean ± SEM of three individual experiments. *<i>P</i><0.05 or **<i>P</i><0.01 vs. NG; ^#<i>P</i><0.05 or ^{# #}<i>P</i><0.05 vs. 5% GS.</p