The glutamine 27 glutamic acid polymorphism of the β<sub>2</sub>‐adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population‐based study in Spain

Sánchez, José Luis González Montes; Proenza, Ana M.; Larrad, M. T. Martinez; Ramis, Joana Maria; Fernández-Pérez, Cristina; Palou, Andreu; Ríos, Manuel Serrano

doi:10.1046/j.1365-2265.2003.01871.x

Cited by 47 publications

(16 citation statements)

References 23 publications

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“…12 studies were excluded because groups were not divided by BMI [6], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23] and one paper was excluded due to the fact that data correlating ADRB2 with obesity were not available[24]. Thus, 18 studies [4], [6], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40] met our inclusion criteria. Of these, 17 papers involving 9,995 subjects genotyped at rs1042714 (all except Angeli et al [39]) and 10 studies [4], [6], [25], [26], [28], [30], [31], [33], [39], [40] including 7,322 subjects genotyped at rs1042713 were included.…”

Section: Resultsmentioning

confidence: 99%

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

Zhang

2014

PLoS ONE

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

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Section: Resultsmentioning

confidence: 99%

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

Zhang

2014

PLoS ONE

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“…22 Obese Spanish men with the Glu27Glu genotype had higher 2 hour post-load glucose concentrations compared with the Gln27Gln genotype. 23 Some studies also have found an association between the Gln allele and higher triglycerides concentrations, 25,26 while other investigators did not find an association between β2-AR and lipid levels. 27-29 …”

Section: Discussionmentioning

confidence: 97%

β-AR Polymorphisms and Glycemic and Lipid Parameters in Hypertensive Individuals Receiving Carvedilol or Metoprolol

Vardeny¹,

Nicholas²,

Andrei³

et al. 2012

Am J Hypertens

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Background β-blocker therapy and β-adrenergic receptor (β-AR) polymorphisms are associated with increases in glucose and lipid levels. We investigated associations of common β1 and β2- AR single nucleotide polymorphisms (SNPs) with metabolic and lipid variables, and examined interactions with β-blocker treatment assignment to affect these parameters. Methods This was a Post hoc analysis of a double-blinded clinical trial of non-diabetic, hypertensive individuals that were randomized to receive carvedilol or metoprolol succinate. Fasting glucose, insulin, and lipid levels were measured at baseline, 3, and after 6 months. Genotypes for β1-AR SNPs Ser49Gly & Gly389Arg and β2-AR Arg16Gly & Gln27Glu were determined. Multivariable mixed models were used to examine associations between β-AR polymorphisms, metabolic parameters, and SNP interactions with β-blocker therapy (pinteraction). Results The 322 subjects were mean (standard deviation) 51.5 (11.2) years old. After 6 months, insulin levels increased by 35.6% on metoprolol but decreased by 9.9% on carvedilol (p=0.015). In univariate models, the Gln27Gln genotype had higher overall insulin levels with β-blockade compared to the Glu27Glu genotype (p=0.006). Both Arg16Gly (p=0.012) and Gln27Glu (p=0.037) SNPs were associated with triglycerides levels. An interaction between the Arg16Gly SNP and treatment was identified (pint=0.048). Conclusions These data suggest that insulin and triglycerides may be influenced by β2-AR polymorphisms in patients taking β–blockers.

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“…These findings show that the genetic background, especially β 2- and β 3-adrenoceptor polymorphisms, are associated with sympathetic nervous system activation, and are important in the pathogenesis of obesity-related hypertension and insulin resistance. Many investigations regarding the relationships between β -adrenoceptor polymorphisms and obesity have been analysed; however, the results are discordant [30–32]. …”

Section: Introductionmentioning

confidence: 99%

Relationships of Adrenoceptor Polymorphisms with Obesity

Masuo

Lambert

2011

Journal of Obesity

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Obesity, hypertension, and type 2 diabetes are rapidly growing public health problems. Heightened sympathetic nerve activity is a well-established observation in obesity, hypertension, and type 2 diabetes. Human obesity, hypertension, and diabetes have strong genetic as well as environmental determinants. Reduced energy expenditure and resting metabolic rate are predictive of weight gain, and the sympathetic nervous system participates in regulating energy balance through thermogenesis. The thermogenic effects of catecholamines in obesity are mainly mediated via the β2, and β3-adrenergic receptors in humans. Further, β2-adrenoceptors importantly influence vascular reactivity and may regulate blood pressure. β-adrenoceptor polymorphisms have also been associated with adrenoceptor desensitization, increased adiposity, insulin resistance, and enhanced sympathetic nervous activity. Many epidemiological studies have shown strong relationships between adrenoceptor polymorphisms and obesity, but the observations have been discordant. This paper will discuss the current topics involving the influence of the sympathetic nervous system and β2- and β3-adrenoceptor polymorphisms in obesity.

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The glutamine 27 glutamic acid polymorphism of the β₂‐adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population‐based study in Spain

Abstract: Our results suggest that the glutamic acid 27 allele of the beta2-adrenoceptor may be a risk factor in men but not in women for the accumulation of visceral fat and for its association with the development of type 2 diabetes mellitus.

Cited by 47 publications

References 23 publications

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

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

β-AR Polymorphisms and Glycemic and Lipid Parameters in Hypertensive Individuals Receiving Carvedilol or Metoprolol

Relationships of Adrenoceptor Polymorphisms with Obesity

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The glutamine 27 glutamic acid polymorphism of the β2‐adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population‐based study in Spain

Abstract: Our results suggest that the glutamic acid 27 allele of the beta2-adrenoceptor may be a risk factor in men but not in women for the accumulation of visceral fat and for its association with the development of type 2 diabetes mellitus.

Cited by 47 publications

References 23 publications

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

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

β-AR Polymorphisms and Glycemic and Lipid Parameters in Hypertensive Individuals Receiving Carvedilol or Metoprolol

Relationships of Adrenoceptor Polymorphisms with Obesity

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The glutamine 27 glutamic acid polymorphism of the β₂‐adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population‐based study in Spain