Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function
Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function
复制标题
DOI：
10.1172/jci119854
复制
发表时间：
1997-12-15
影响因子：
15.9
通讯作者：
Arner, P
中科院分区：
文献类型：
--
作者：
Large, V;Hellström, L;Arner, P
儿茶酚胺在能量消耗的调节中起核心作用，部分是通过脂肪细胞中的脂解刺激脂质动员。β-2肾上腺素受体（BAR-2）是人类脂肪细胞中的主要脂解受体。为了确定该受体的密码子16、27和164中的已知多态性是否在肥胖和皮下脂肪细胞BAR-2脂解功能中起作用，我们调查了一组140名女性，她们的体脂量有很大的差异，只有密码子16和27的多态性在研究人群中很常见，Gln 27 Glu多态性与肥胖显著相关，肥胖的相对危险度接近7，比值比接近10。Glu 27纯合子的平均脂肪量超过20 kg，脂肪细胞比对照组大50%。然而，未观察到与BAR-2功能变化的显著相关性。Arg 16 Gly多态性与BAR-2功能改变相关，Gly 16携带者显示激动剂敏感性增加5倍，而BAR-2表达无任何变化。这些发现表明，人BAR-2基因的遗传变异性可能对肥胖、能量消耗和脂肪组织中的脂肪分解BAR-2功能非常重要，至少在女性中是如此。
Catecholamines play a central role in the regulation of energy expenditure, in part by stimulating lipid mobilization through lipolysis in fat cells, The beta-2 adrenoceptor (BAR-2) is a major lipolytic receptor in human fat cells, To determine whether known polymorphisms in codons 16, 27, and 164 of this receptor play a role in obesity and subcutaneous adipocyte BAR-2 lipolytic function, we investigated a group of 140 women with a large variation in body fat mass, Only the polymorphisms in codons 16 and 27 were common in the study population, The Gln27Glu polymorphism was markedly associated with obesity with a relative risk for obesity of similar to 7 and an odds ratio of similar to 10. Homozygotes for Glu27 had an average fat mass excess of 20 kg and similar to 50% larger fat cells than controls, However, no significant association with changes in BAR-2 function was observed, The Arg16Gly polymorphism was associated with altered BAR-2 function with Gly16 carriers showing a fivefold increased agonist sensitivity and without any change in BAR-2 expression, However, it was not significantly linked with obesity, These findings suggest that genetic variability in the human BAR-2 gene could be of major importance for obesity, energy expenditure, and lipolytic BAR-2 function in adipose tissue, at least in women.