WRN gene 1367 Arg allele protects against development of type 2 diabetes mellitus

WRN gene 1367 Arg allele protects against development of type 2 diabetes mellitus
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DOI:
10.1016/j.diabres.2005.01.012
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发表时间:
2005-09-01
影响因子:
5.1
通讯作者:
Oka, Y
Oka, Y
中科院分区:
医学3区
文献类型:
--
作者:
Hirai, M;Suzuki, S;Oka, Y

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Werner‘S综合征是由wrn基因突变引起的常染色体隐性遗传病,可导致DNA修复失败,加速衰老。据报道,在日本,1367位氨基酸Cys(TTG)/Arg(CTG)的多态可降低心肌梗死的风险。我们研究了该基因多态性在2型糖尿病中的可能作用。对272例2型糖尿病患者(年龄64.5±11.1岁)进行WRN基因多态性分析,发现Cys/Arg组年龄大于Cys/Arg组(p=0.021),且Cys/Arg组初诊年龄大于Cys/Cys组(p=0.011)。经Kaplan-Meier方法分析,两组间的无糖尿病存活率有显著差异(p=0.0125),与Cys/Arg组相比,Cys/Arg组的生存曲线右移。糖尿病组(n=272)和非糖尿病组(n=171,年龄66.0+/-8.0)等位基因频率差异无统计学意义。这些结果表明,WRN基因的1367Arg等位基因对日本人2型糖尿病的发生具有保护作用。(C)2005爱思唯尔爱尔兰有限公司。保留所有权利。
Werner ' s syndrome is an autosomal recessive disease caused by mutation of the WRN gene, which may lead to DNA repair failure and acceleration of aging. A polymorphism at amino acid 1367 Cys (TTG)/Arg (CTG) reportedly reduces the risk of myocardial infarction in Japanese. We studied the possible involvement of this polymorphism in type 2 diabetes. When polymorphism of the WRN gene was analyzed in 272 randomly recruited type 2 diabetic subjects (age 64.5 +/- 11. 1), we found those with Cys/Arg to be older than those with Cys/Cys (p = 0.021) and that the age at diagnosis of diabetes was greater in Cys/ Arg than in Cys/Cys subjects (p = 0.011). Diabetes-free survival rate over the age, analyzed by Kaplan-Meier method, differed significantly between these two genotype groups (p = 0.0125) and the survival curve was shifted to the right in the Cys/Arg group as compared to the Cys/Cys group. No difference in allele frequency was observed between our diabetic (n = 272) and non-diabetic subjects (n = 171, age 66.0 +/- 8.0). These results suggest that the 1367 Arg allele of the WRN gene protects against the development of type 2 diabetes mellitus in Japanese. (c) 2005 Elsevier Ireland Ltd. All rights reserved.