Song Yiqing, You Nai-chieh, Hsu Yi-Hsiang, Sul James, Wang Lin, Tinker Lesley, Eaton Charles B, Liu Simin
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston , MA 02215, USA.
Hum Mol Genet. 2007 Dec 1;16(23):2960-71. doi: 10.1093/hmg/ddm256. Epub 2007 Sep 12.
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.
钙蛋白酶-10（CAPN10）蛋白可能在葡萄糖代谢、胰腺β细胞胰岛素分泌和产热过程中发挥作用。新出现的证据表明，CAPN10基因变异在2型糖尿病（T2DM）风险中起作用。然而，先前的关联研究仅集中在最初报道的几个变异上，且结果不一致。我们进行了一项大型巢式病例对照研究，以全面调查来自女性健康倡议观察性研究的50-79岁绝经后女性中，CAPN10基因常见变异与T2DM风险之间的关联。在对244个随机选择的对照样本（四个种族群体各61个）进行全面筛查后，我们在CAPN10中总共选择了12个跨越91 kb的标签单核苷酸多态性（tSNP），并在1543例糖尿病病例和2132例匹配对照中对其进行基因分型（包括白人968例病例和968例对照、黑人366例和732例、西班牙裔152例和303例、亚洲/太平洋岛民98例和195例）。在整个研究样本或任何特定种族群体中，任何单个tSNP与T2DM之间均无显著关联。也没有证据表明常见的CAPN10单倍型与糖尿病风险之间存在关联（总体常见单倍型风险差异的全局检验P = 0.31，第1组单倍型P = 0.44，第2组单倍型P = 0.37）。总之，在我们这个种族多样的大型绝经后女性队列中，我们未观察到CAPN10基因常见SNP或单倍型与糖尿病风险有任何显著关联。
