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. 2000 Oct;106(7):R69-73.
doi: 10.1172/JCI10665.

A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance

L J Baier  1 , P A Permana, X Yang, R E Pratley, R L Hanson, G Q Shen, D Mott, W C Knowler, N J Cox, Y Horikawa, N Oda, G I Bell, C Bogardus
Affiliations

A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance

L J Baier et al. J Clin Invest. 2000 Oct.

Abstract

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 G/G genotype was not 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 CAPN10 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.

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Figures

Figure 1
Figure 1
Association between CAPN10 mRNA expression and UCSNP-43 genotype and 24-hour carbohydrate oxidation rates. (a) CAPN10 mRNA expression, as measured by real-time PCR, in skeletal muscle of nondiabetic males representing G/G (n = 8), G/A (n = 7), and A/A (n = 3) UCSNP-43 genotypes. The levels of CAPN10 transcripts are normalized to the levels of endogenous β-actin. The mean transcript level was significantly lower in the G/G homozygotes when compared with the G/A and A/A groups (P = 0.02). (b) The relationship between CAPN10 transcript levels in skeletal muscle and 24-hour carbohydrate oxidation rates (r = 0.79). Carbohydrate oxidation rates are adjusted for age, percentage of body fat, and energy balance.
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