β2- and β3-adrenergic receptor polymorphisms are related to the onset of weight gain and blood pressure elevation over 5 years
β2- and β3-adrenergic receptor polymorphisms are related to the onset of weight gain and blood pressure elevation over 5 years
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DOI：
10.1161/circulationaha.104.519652
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发表时间：
2005-06-28
期刊：
影响因子：
37.8
通讯作者：
Tuck, ML
中科院分区：
文献类型：
--
作者：
Masuo, K;Katsuya, T;Tuck, ML
背景-肥胖基因是肥胖相关疾病的候选基因，如高血压.β（2）-和β（3）-肾上腺素能受体的功能多态性已被报道与高血压和肥胖有关。方法和结果-为了纵向阐明β-肾上腺素能受体多态性改变与体重增加、血压（BP）升高和交感神经活性（通过血浆去甲肾上腺素水平测量）的相关性，我们研究了160名年轻、非肥胖、血压正常的男性在5年的时间里，定期测量体重、血压、血浆去甲肾上腺素水平和β（2）-肾上腺素能（Arg 16 Gly，Gln 27 Glu）和β（3）-肾上腺素能（Trp 64 Arg）受体多态性的变化。体重增加和血压升高定义为5年内体重指数或平均血压较入门水平增加≥ 10%。Arg 16 Gly的Gly 16等位基因的存在与5年期间体重增加和血压升高的频率较高相关。携带Gln 27 Glu的Glu 27等位基因和Trp 64 Arg的Trp 64等位基因的受试者血压升高的频率较高。显著较高水平的血浆去甲肾上腺素在入口处，并在第5年观察到与Gly 16等位基因的Arg 16 Gly和Glu 27等位基因的Gln27Glu.Conclusions相比，那些没有Gly 16或Glu 27等位基因的受试者，这些结果表明，Gly 16等位基因与更大的体重增加和血压升高。此外，Glu 27和Trp 64等位基因与血压升高有关。携带与体重增加和血压升高相关的β（2）-多态性的受试者也具有较高的血浆去甲肾上腺素水平，该水平在体重增加和血压升高之前存在。这些发现表明，β（2）-肾上腺素能受体多态性与交感神经活动增强相关，可以预测未来肥胖和高血压的发病，如5年纵向研究所示。
Background - The genes responsible for obesity are candidate genes for obesity- related diseases, such as hypertension. Functional polymorphisms in the beta(2)- and beta(3)- adrenergic receptors have been reported to be associated with hypertension and obesity.Methods and Results - To longitudinally clarify the relevance to alterations in beta- adrenergic receptor polymorphisms related to weight gain, blood pressure ( BP) elevation, and sympathetic nerve activity as measured by plasma norepinephrine level, we studied 160 young, nonobese, normotensive men. Changes in body weight, BP, plasma norepinephrine levels, and beta(2)- adrenergic ( Arg16Gly, Gln27Glu) and beta(3)- adrenergic ( Trp64Arg) receptor polymorphisms were measured periodically over a 5- year period. Weight gain and BP elevation were defined as >= 10% increases from entry levels over 5 years in body mass index or mean BP. The presence of the Gly16 allele of Arg16Gly was associated with a higher frequency of weight gain and BP elevation over the 5- year period. The subjects carrying the Glu27 allele of Gln27Glu and the Trp64 allele of Trp64Arg had a higher frequency of BP elevation. Significantly higher levels of plasma norepinephrine at entry and at year 5 were observed in the subjects with the Gly16 allele of Arg16Gly and the Glu27 allele of Gln27Glu compared with those without the Gly16 or the Glu27 alleles.Conclusions - These results demonstrate that the Gly16 allele is related to greater weight gain and BP elevation. Additionally, Glu27 and Trp64 alleles are linked to BP elevation. The subjects carrying the beta(2)- polymorphisms linked to weight gain and BP elevation also have higher plasma norepinephrine levels that are present at entry before weight gain and BP elevation. These findings suggest that beta(2)- adrenergic receptor polymorphisms in association with a heightened sympathetic nerve activity could predict the future onset of obesity and hypertension, as shown in the 5- year longitudinal study.