A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance
A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance
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DOI：
10.1172/jci10665
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发表时间：
2000-10-01
影响因子：
15.9
通讯作者：
Bogardus, C
中科院分区：
文献类型：
--
作者：
Baier, LJ;Permana, PA;Bogardus, C
先前在墨西哥裔美国人中进行的连锁研究将2型糖尿病的主要易感基因NIDDM 1定位于染色体2 q。最近发现与2型糖尿病相关的证据与CAPN 10基因内的常见G->A多态性（UCSNP-43）有关。高危基因型为UCSNP-43 G等位基因纯合子。在本研究中，Pima印第安人中，UCSNP-43 GIG基因型与2型糖尿病患病率增加无关。然而，在UCSNP-43上具有G/G基因型的具有正常葡萄糖耐量的皮马印第安人被发现具有吸收后和胰岛素刺激的葡萄糖周转率降低，这似乎是由于葡萄糖氧化率降低。此外，G/G纯合子被发现在其骨骼肌中C4 PN 10 mRNA表达减少。胰岛素介导的葡萄糖转换率降低或胰岛素抵抗是CAPN 10多态性可能增加老年人对2型糖尿病易感性的一种机制。
Previous linkage studies in Mexican-Americans localized a major susceptibility locus for type 2 diabetes, NIDDM1, to chromosome 2q. This evidence for linkage to type 2 diabetes was recently found to be associated with a common G->A polymorphism (UCSNP-43) within the CAPN10 gene. The at-risk genotype was homozygous for the UCSNP-43 G allele. In the present study among Pima Indians, the UCSNP-43 GIG genotype was nor associated with an increased prevalence of type 2 diabetes. However, Pima Indians with normal glucose tolerance, who have a G/G genotype at UCSNP-43, were found to have decreased rates of postabsorptive and insulin-stimulated glucose turnover that appear to result from decreased rates of glucose oxidation. In addition, G/G homozygotes were found to have reduced C4PN10 mRNA expression in their skeletal muscle. A decreased rate of insulin-mediated glucose turnover, or insulin resistance, is one mechanism by which the polymorphism in CAPN10 may increase susceptibility to type 2 diabetes mellitus in older persons.