Genetic variation in UCP2 (uncoupling protein-2) is associated with energy metabolism in Pima Indians
Genetic variation in UCP2 (uncoupling protein-2) is associated with energy metabolism in Pima Indians
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DOI：
10.1007/s00125-005-1934-9
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发表时间：
2005-11-01
期刊：
影响因子：
8.2
通讯作者：
Baier, LJ
中科院分区：
文献类型：
--
作者：
Kovacs, P;Ma, L;Baier, LJ
目的/假设：解偶联蛋白-2（UCP 2）被认为在胰岛素分泌和肥胖的发展中起作用。在这项研究中，我们调查了UCP 2基因变异对2型糖尿病和肥胖的影响，以及与这些疾病相关的代谢表型，在皮马印第安人。研究方法：UCP 2的编码区和非翻译区，以及大约1 kb的5'上游区，在83个极端肥胖的皮马印第安人的DNA样本中进行了测序，这些印第安人不是一级亲属。结果如下：确定了五种变体：（1）5'上游区的-866G/A;（2）外显子2中的G/A;（3）导致外显子4中Ala 55 Val取代的C/T;和（4，5）3'非翻译区中的两个插入/缺失（ins/del; 45-bp和3-bp）。在83例DNA测序的受试者中，-866G/A与Ala 55 Val和3-bp ins/del多态性完全一致。外显子2的G/A多态性极为罕见。为了捕获该基因的常见变异以进行关联分析，还对864名纯种皮马印第安人的-866G/A变异（作为Ala 55 Val和3-bp ins/del多态性的代表）和45-bp ins/del进行了基因分型。这些变异都与2型糖尿病或体重指数无关。然而，在一个185名接受了详细代谢测量的受试者的亚组中，这些变异与在人体代谢室中测量的24小时能量消耗相关（在调整年龄，性别，家庭成员，无脂肪质量和脂肪质量后，45 bp ins/del的p=0.007，-866G/A的p=0.03）。结论/解释：我们的数据表明，UCP 2的变异可能在能量代谢中发挥作用，但该基因对皮马印第安人2型糖尿病和/或肥胖的病因学没有显着贡献。
Aims/hypothesis: Uncoupling protein-2 (UCP2) is thought to play a role in insulin secretion and the development of obesity. In this study, we investigated the effects of genetic variation in UCP2 on type 2 diabetes and obesity, as well as on metabolic phenotypes related to these diseases, in Pima Indians. Methods: The coding and untranslated regions of UCP2, and approximately 1 kb of the 5' upstream region, were sequenced in DNA samples taken from 83 extremely obese Pima Indians who were not first-degree relatives. Results: Five variants were identified: (1) a -866G/A in the 5' upstream region; (2) a G/A in exon 2; (3) a C/T resulting in an Ala55Val substitution in exon 4; and (4, 5) two insertion/deletions (ins/del; 45-bp and 3-bp) in the 3' untranslated region. Among the 83 subjects whose DNA was sequenced, the -866G/A was in complete genotypic concordance with the Ala55Val and the 3-bp ins/del polymorphism. The G/A polymorphism in exon 2 was extremely rare. To capture the common variation in this gene for association analyses, the -866G/A variant (as a representative of Ala55Val and the 3-bp ins/del polymorphism) and the 45-bp ins/del were also genotyped for 864 full-blooded Pima Indians. Neither of these variants was associated with type 2 diabetes or body mass index. However, in a subgroup of 185 subjects who had undergone detailed metabolic measurements, these variants were associated with 24-h energy expenditure as measured in a human metabolic chamber (p=0.007 for the 45-bp ins/del and p=0.03 for the -866G/A after adjusting for age, sex, family membership, fat-free mass and fat mass). Conclusions/interpretation: Our data indicate that variation in UCP2 may play a role in energy metabolism, but this gene does not contribute significantly to the aetiology of type 2 diabetes and/or obesity in Pima Indians.