Common genetic variation in calpain-10 gene (CAPN10) and diabetes risk in a multi-ethnic cohort of American postmenopausal women
Common genetic variation in calpain-10 gene (CAPN10) and diabetes risk in a multi-ethnic cohort of American postmenopausal women
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DOI：
10.1093/hmg/ddm256
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发表时间：
2007-12-01
影响因子：
3.5
通讯作者：
Liu, Simin
中科院分区：
文献类型：
--
作者：
Song, Yiqing;You, Nai-Chieh;Liu, Simin
钙蛋白酶-10（CAPN 10）蛋白可能在葡萄糖代谢、胰腺β细胞胰岛素分泌和产热中发挥作用。新出现的证据表明CAPN 10遗传变异在2型糖尿病（T2 DM）风险中的作用。然而，以前的关联研究只集中在最初报告的几个变体上，并提供了不一致的结果。我们进行了一项大型巢式病例对照研究，以全面调查妇女健康倡议观察性研究中年龄在50-79岁的绝经后妇女中CAPN 10基因常见变异与T2 DM风险之间的关系。在244个随机选择的对照样本中进行全面筛选后，（4个种族各61例），我们在1543例糖尿病患者和2132例对照者中选择了CAPN 10中12个跨越91 kb的标记单核苷酸多态性（tSNPs）进行基因分型（包括968例和968例白人对照，366例和732例黑人，152例和303例西班牙裔，98例和195例亚洲/太平洋岛民）。在整个研究样本或任何特定种族群体中，任何个体tSNP与T2 DM之间均无显著相关性。也没有任何证据表明常见CAPN 10单倍型与糖尿病风险之间存在关联（风险差异的全球检验结果为：总体常见单倍型P=0.31，区组1中单倍型P=0.44，区组2中单倍型P=0.37）。总之，我们没有观察到任何显着的关联，共同的SNPs或单倍型跨CAPN 10基因与糖尿病的风险，在我们的大型和种族多样化的队列绝经后妇女。
Calpain-10 (CAPN10) protein may play a role in glucose metabolisms, pancreatic beta-cell insulin secretion and thermogenesis. Emerging evidence has implicated a role of CAPN10 genetic variants in the risk of type 2 diabetes mellitus (T2DM). Previous association studies, however, have focussed only on several variants initially reported and provided inconsistent results. We conducted a large nested case-control study to comprehensively investigate the associations between common variations in CAPN10 gene and T2DM risk among postmenopausal women aged 50-79 years from the Women's Health Initiative Observational Study. After comprehensive screening in 244 randomly chosen control samples (n=61 for each of four ethnic groups), we selected a total of 12 tagging single nucleotide polymorphisms (tSNPs) spanning 91 kb in CAPN10 and genotyped them in 1543 diabetes cases and 2132 matched controls (including 968 cases and 968 controls for whites, 366 and 732 for blacks, 152 and 303 for Hispanics and 98 and 195 for Asian/Pacific Islanders). There were no significant associations between any individual tSNP and T2DM, within either the full study sample or any specific ethnic group. Nor was there any evidence of association between common CAPN10 haplotypes and diabetes risk (global tests for differences in risk were P=0.31 for overall common haplotypes, P=0.44 for haplotypes in block 1 and P=0.37 for haplotypes in block 2). In conclusion, we did not observe any significant associations of the common SNPs or haplotypes across the CAPN10 gene with diabetes risk in our large and ethnically diverse cohort of postmenopausal women.