Gjesing A P, Andersen G, Burgdorf K S, Borch-Johnsen K, Jørgensen T, Hansen T, Pedersen O
Steno Diabetes Center, Niels Steensens Vej 2, NSH2.16, 2820, Gentofte, Denmark.
Diabetologia. 2007 Mar;50(3):563-8. doi: 10.1007/s00125-006-0578-8. Epub 2007 Jan 13.
AIMS/HYPOTHESIS: Functional and common Arg16Gly and Gln27Glu polymorphisms have been identified in ADRB2, the gene encoding the beta2-adrenergic receptor. These variants have previously been examined for association with obesity, hypertension and diabetes with inconclusive results.
We investigated both of these variants in 7,808 unrelated, middle-aged white people for their association with obesity in a case-control study, quantitative trait analysis and meta-analysis. Moreover, both variants were investigated for their potential influence on measures of hypertension and type 2 diabetes by case-control and quantitative trait analyses.
The present study did not find consistent evidence for an association of these beta2-adrenergic receptor variants with obesity or hypertension; neither did the quantitative trait analyses show any effect of the variants on obesity-related traits. However, both the Gly allele of the Arg16Gly variant and the Glu allele of the Gln27Glu variant showed nominal association with systolic blood pressure. Furthermore, there was a nominal association of the Arg16 allele frequency and genotype distribution with type 2 diabetes; however, no influence on quantitative biochemical phenotypes related to type 2 diabetes was found. A nominal association of the Arg/Gly genotype with the metabolic syndrome was also observed (p=0.003). Logistic regression analyses provided no evidence of a synergistic or an additive effect of these variants on obesity, hypertension or diabetes.
CONCLUSIONS/INTERPRETATION: After studying 7,808 middle-aged white subjects, we were unable to demonstrate any consistent associations between two common amino acid polymorphisms of the beta2-adrenergic receptor and obesity, hypertension or type 2 diabetes.
目的/假设：在编码β2-肾上腺素能受体的基因ADRB2中已鉴定出功能性及常见的Arg16Gly和Gln27Glu多态性。此前已对这些变体与肥胖症、高血压和糖尿病的关联进行了研究，但结果尚无定论。
在一项病例对照研究、数量性状分析和荟萃分析中，我们调查了7808名无亲属关系的中年白人中这两种变体与肥胖症的关联。此外，通过病例对照和数量性状分析，研究了这两种变体对高血压和2型糖尿病指标的潜在影响。
本研究未发现这些β2-肾上腺素能受体变体与肥胖症或高血压存在一致关联的证据；数量性状分析也未显示这些变体对肥胖相关性状有任何影响。然而，Arg16Gly变体的Gly等位基因和Gln27Glu变体的Glu等位基因与收缩压呈名义上的关联。此外，Arg16等位基因频率和基因型分布与2型糖尿病呈名义上的关联；然而，未发现对与2型糖尿病相关的定量生化表型有影响。还观察到Arg/Gly基因型与代谢综合征存在名义上的关联（p = 0.003）。逻辑回归分析未提供这些变体对肥胖症、高血压或糖尿病有协同或累加效应的证据。
结论/解读：在对7808名中年白人受试者进行研究后，我们未能证明β2-肾上腺素能受体的两种常见氨基酸多态性与肥胖症、高血压或2型糖尿病之间存在任何一致的关联。
