Dataset Information

Association of Gln27Glu and Arg16Gly polymorphisms in Beta2-adrenergic receptor gene with obesity susceptibility: a meta-analysis.

ABSTRACT:

Background

The beta2-adrenergic receptor (ADRB2) gene polymorphism has been implicated in susceptibility to obesity, but study results are still controversial.

Objective

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.

Methods

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", "?2-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.

Results

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, I2?=?49%, P?=?0.009) and the dominant model (Gln/Glu + Glu/Glu vs. Gln/Gln: OR: 1.2, 95% CI: 1.00-1.44, I2?=?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.

Conclusion

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.

SUBMITTER: Zhang H

PROVIDER: S-EPMC4069060 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of Gln27Glu and Arg16Gly polymorphisms in Beta2-adrenergic receptor gene with obesity susceptibility: a meta-analysis.

Zhang Hongxiu H Wu Jie J Yu Lipeng L

PloS one 20140624 6

<h4>Background</h4>The beta2-adrenergic receptor (ADRB2) gene polymorphism has been implicated in susceptibility to obesity, but study results are still controversial.<h4>Objective</h4>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.<h4>Methods</h4>The PubMed (1950-2014), Embase (1974-2014), and China National Knowledge Infrastructure (CNKI, 1994-2 ...[more]

PMID: 24960039

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Project description:BackgroundAsthma is caused by both environmental and genetic factors. The ADRB2 gene, which encodes the beta 2-adrenergic receptor, is one of the most extensively studied genes with respect to asthma prevalence and severity. The Arg16Gly (+46A > G) and Gln27Glu (+79C > G) polymorphisms in the ADRB2 gene cause changes in the amino acids flanking the receptor ligand site, altering the response to bronchodilators and the risk of asthma through complex pathways. The ADRB2 polymorphisms affect beta-adrenergic bronchodilator action and are a tool to identify at-risk populations.ObjectiveTo determine the frequency of these two polymorphisms in allergic asthma patients and healthy subjects and to correlate these data with the occurrence and severity of asthma.MethodsEighty-eight allergic asthma patients and 141 healthy subjects were included in this study. The ADRB2 polymorphisms were analyzed using the amplification-refractory mutation system - polymerase chain reaction (ARMS-PCR) technique. The statistical analysis was performed with the SPSS 21.0 software using the Fisher's Exact and χ2 tests.ResultsThe ADRB2 polymorphisms were associated with asthma occurrence. The Arg16Arg, Gln27Gln and Gln27Glu genotypes were risk factors; the odds ratios were 6.782 (CI = 3.07 to 16.03), 2.120 (CI = 1.22 to 3.71) and 8.096 (CI = 3.90 to 17.77), respectively. For the Gly16Gly and Glu27Glu genotypes, the odds ratios were 0.312 (CI = 0.17 to 0.56) and 0.084 (CI = 0.04 to 0.17), respectively. The haplotype analysis showed that there were associations between the following groups: Arg16Arg-Gln27Gln (OR = 5.108, CI = 1.82 to 16.37), Gly16Gly-Glu27Glu (OR = 2.816, CI = 1.25 to 6.54), Arg16Gly-Gln27Glu (OR = 0.048, CI = 0.01 to 0.14) and Gly16Gly-Gln27Glu (OR = 0.1036, CI = 0.02 to 0.39). The polymorphism Gln27Glu was associated with asthma severity, as the Gln27Gln genotype was a risk factor for severe asthma (OR = 2.798, CI = 1.099 to 6.674) and the Gln27Glu genotype was a protective factor for mild (OR = 3.063, CI = 1.037 to 9.041) and severe (OR = 0.182, CI = 0.048 to 0.691) asthma.ConclusionsThe Arg16Gly and Gln27Glu polymorphisms in the ADRB2 gene are associated with asthma presence and severity.

Project description:Genes involved in the regulation of catecholamine function may be important in obesity because of the role catecholamines play in energy expenditure and lipolysis. To determine if common single nucleotide polymorphisms (SNPs) in beta(1)-adrenergic receptor (ADRB1), beta(2)-adrenergic receptor (ADRB2), beta(3)-adrenergic receptor (ADRB3), and alpha(2)-adrenergic receptor (ADRA2A) genes associate with obesity and metabolic alterations, we recruited 74 healthy African American and 161 white men and women (age, 18-49 years) to participate in this case-control genetic association study. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. Associations between genotype and body mass index (BMI), percentage of body fat (by measuring skinfold thickness in 7 different sites), fasting (12-hour) plasma glucose, insulin, potassium concentrations, glycated hemoglobin, and insulin resistance (homeostasis model assessment [HOMA(IR)] score) were performed. Among whites, the ADRB1 Arg389-->Gly variant associated with insulin concentrations and HOMA(IR): mean +/- SD values for insulin and HOMA(IR) in Arg389 homozygotes and carriers of the Gly were 10 +/- 7.0 and 12 +/- 9.4 micro IU/mL (P = .02) and 2.1 +/- 1.7 and 2.6 +/- 2.2 (P = .057), respectively. Systolic blood pressure was higher in whites for carriers of the ADBR1 Ser49 compared to Gly49 homozygotes (124 +/- 12.6 vs 119 +/- 11.3 mm Hg, respectively; P = .02). Subsequent analysis revealed that these associations were attributable to a higher BMI among obese participants. The ADRA2A G1780A SNP associated with BMI and percentage of body fat in African Americans (P = .05). Interactions were detected between ADRA2A C-1291G and ADRB2 Gln27-->Glu variants for obesity in African Americans and between ADRA2A C-1291G SNP and ADBR1 haplotype for obesity in whites. We conclude that common SNPs in adrenergic receptor genes may be important susceptibility loci for obesity and related alterations. Because of the limited size of our populations, our results should be interpreted with caution and should be replicated in larger populations.

Project description:Aims/hypothesisHomozygosity for glycine at codon 16 (GlyGly) of the ?(2)-adrenergic receptor may alter receptor sensitivity upon chronic stimulation and has been implicated in the pathogenesis of hypoglycaemia unawareness. We compared the effect of antecedent hypoglycaemia on ?(2)-adrenergic receptor sensitivity between GlyGly participants and those with arginine 16 homozygosity (ArgArg) for the ?(2)-adrenergic receptor.MethodsWe enrolled 16 healthy participants, who were either GlyGly (n?=?8) or ArgArg (n?=?8). They participated randomly in two 2 day experiments. Day 1 consisted of two 2-h hyperinsulinaemic hypoglycaemic (2.8 mmol/l) or euglycaemic (4.8 mmol/l) glucose clamps. On day 2, we measured the forearm vasodilator response to the ?(2)-adrenergic receptor agonist salbutamol and the dose of isoprenaline required to increase the heart rate by 25 bpm (IC(25)).ResultsThe vasodilator response to salbutamol tended to be greater after antecedent hypoglycaemia than after euglycaemia (p?=?0.078), consistent with increased ?(2)-adrenergic receptor sensitivity. This effect was driven by a significant increase in ?(2)-adrenergic receptor sensitivity following hypoglycaemia compared with euglycaemia in ArgArg participants (p?=?0.019), whereas no such effect was observed in the GlyGly participants. Antecedent hypoglycaemia tended to decrease the IC(25) in ArgArg participants, whereas the reverse occurred in the GlyGly participants (GlyGly vs ArgArg group p?=?0.047).Conclusion/interpretationAntecedent hypoglycaemia did not affect ?(2)-adrenergic receptor sensitivity in healthy GlyGly participants, but increased it in ArgArg participants. If these results also hold for participants with type 1 diabetes, such an increase in ?(2)-adrenergic receptor sensitivity may potentially reduce the risk of repeated hypoglycaemia and the subsequent development of hypoglycaemia unawareness in ArgArg diabetic participants.Trial registrationClinicalTrials.gov NCT00160056.

Dataset Information

Association of Gln27Glu and Arg16Gly polymorphisms in Beta2-adrenergic receptor gene with obesity susceptibility: a meta-analysis.

Background

Objective

Methods

Results

Conclusion

Publications

Association of Gln27Glu and Arg16Gly polymorphisms in Beta2-adrenergic receptor gene with obesity susceptibility: a meta-analysis.

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