Studies of the common DIO2 Thr92Ala polymorphism and metabolic phenotypes in 7342 Danish white subjects
Studies of the common DIO2 Thr92Ala polymorphism and metabolic phenotypes in 7342 Danish white subjects
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DOI：
10.1210/jc.2006-1958
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发表时间：
2007-01-01
影响因子：
5.8
通讯作者：
Pedersen, Oluf
中科院分区：
文献类型：
--
作者：
Grarup, Niels;Andersen, Mette K.;Pedersen, Oluf
内容：2型碘甲状腺原氨酸脱碘酶（D2）催化T-4转化为甲状腺激素的活性形式，甲状腺激素是产热和葡萄糖代谢的关键调节剂。A Thr 92 Ala多态性基因编码的D2（DIO 2）已被报道与insulin resistance.Objective：本研究的目的是评估的DIO 2 Thr 92 Ala变异的影响2型糖尿病（T2 D），肥胖，和相关的定量代谢性状，包括胰岛素抵抗的措施。由于DIO 2是通过β-肾上腺素能受体依赖性途径激活的，我们进一步假设ADRB基因的变异与DIO 2 Thr 92 Ala变体相互作用以影响代谢特征。设计和患者：DIO 2多态性在总共7342名白色受试者中进行基因分型，包括1405名T2 D患者。我们没有发现DIO 2 Thr 92 Ala多态性与T2 D或肥胖有显著关联。在纯合子Ala 92等位基因携带者中，我们观察到基因型与口服葡萄糖耐量试验期间血清胰岛素曲线下面积增加（P = 0.03）和空腹血糖升高（P = 0.02）之间存在名义上的显著相关性，后者在双隐性模型中通过与ADRB 2 Gly 16 Arg变异体的上位性而得到加强（P = 0.004）。然而，经过排列程序，进行纠正多假设检验，协会没有达到研究范围内的significant.Conclusions：DIO 2 Thr 92 Ala变异不赋予2型糖尿病，肥胖症，或胰岛素抵抗的风险增加。
Context: The type 2 iodothyronine deiodinase (D2) catalyzes the conversion of T-4 to the active form of thyroid hormone, which is a critical regulator of thermogenesis and glucose metabolism. A Thr92Ala polymorphism in the gene encoding D2 (DIO2) has been reported to associate with insulin resistance.Objective: The aim of the present study was to assess the impact of the DIO2 Thr92Ala variant on type 2 diabetes (T2D), obesity, and related quantitative metabolic traits including measures of insulin resistance. Because DIO2 is activated through a beta-adrenergic receptor-dependent pathway, we further hypothesized that variation in the ADRB genes interacts with DIO2 Thr92Ala variant to influence metabolic traits.Design and Patients: The DIO2 polymorphism was genotyped in a total of 7342 white subjects including 1405 T2D patients.Results: We detected no significant association of the DIO2 Thr92Ala polymorphism with T2D or obesity. We observed nominal significant associations of genotype with increased area under the serum insulin curve during an oral glucose tolerance test (P = 0.03) and elevated fasting plasma glucose ( P = 0.02) in homozygous Ala92 allele carriers, the latter strengthened by epistasis with the ADRB2 Gly16Arg variant in a double recessive model ( P = 0.004). However, after permutation procedure, performed to correct for multiple hypothesis testing, the associations did not reach study-wide significance.Conclusions: The DIO2 Thr92Ala variant does not confer an increased risk of T2D, obesity, or insulin resistance.