Mutations in the Small Heterodimer Partner Gene Increase Morbidity Risk in Japanese Type 2 Diabetes Patients
Mutations in the Small Heterodimer Partner Gene Increase Morbidity Risk in Japanese Type 2 Diabetes Patients
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DOI：
10.1002/humu.20865
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发表时间：
2008-11-01
期刊：
影响因子：
3.9
通讯作者：
Takeda, Jun
中科院分区：
文献类型：
--
作者：
Enya, Mayumi;Horikawa, Yukio;Takeda, Jun
小异源二聚体伴侣基因（NR 0 B2;别名SHP）突变与日本儿童的高出生体重和轻度肥胖相关。SHP突变也可能与后来的肥胖和胰岛素抵抗综合征有关，后者会诱发糖尿病。为了研究这种可能性，我们评估了日本2型糖尿病患者和非2型糖尿病患者中SHP突变的患病率以及突变蛋白的功能特性。对805名糖尿病患者和752名非糖尿病对照者的SHP的两个外显子和侧翼序列进行直接测序，在44名受试者中发现了15种不同的突变，包括6种新突变。对突变蛋白的功能分析显示，其中9个突变的活性显著降低。在糖尿病组的19名患者（2.4%）和对照组的6名受试者（0.8%）中发现了活性降低的突变。经性别和年龄调整后，DM和对照受试者之间的频率差异具有统计学意义（P=0.029，比值比2.67，95% CI 1.05 - 6.81，1-β =0.91）。我们的结论是，与儿童期轻度肥胖相关的SHP突变增加了日本人日后患2型糖尿病的易感性。(C)2008 Wiley-Liss，Inc.
Mutations in the small heterodimer partner gene (NR0B2; alias SHP) are associated with high birth weight and mild obesity in Japanese children. SHP mutations may also be associated with later obesity and insulin resistance syndrome that induces diabetes. To investigate this possibility, the prevalence of SHP mutations in Japanese with and without type 2 diabetes mellitus and the functional properties of the mutant proteins were evaluated. Direct sequencing of two exons and flanking sequences of SHP in 805 diabetic patients and 752 non-diabetic controls identified 15 different mutations in 44 subjects, including 6 novel mutations. Functional analyses of the mutant proteins revealed significantly reduced activity of nine of the mutations. Mutations with reduced activity were found in 19 patients (2.4%) in the diabetic group and in 6 subjects (0.8%) in the control group. The frequency difference between DM and control subjects adjusted for sex and age was statistically significant (P=0.029, odds ratio 2.67, 95% CI 1.05 - 6.81, 1-beta=0.91). We conclude that SHP mutations associated with mild obesity in childhood increase susceptibility to type 2 diabetes in later life in Japanese. (C) 2008 Wiley-Liss, Inc.