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

Baier LJ, Permana PA, Yang X, Pratley RE, Hanson RL, Shen GQ, Mott D, Knowler WC, Cox NJ, Horikawa Y, Oda N, Bell GI, Bogardus C
J Clin Invest. 2000 106 (7): R69-73

PMID: 11018080 · PMCID: PMC387246 · DOI:10.1172/JCI10665

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.

MeSH Terms (22)

Adolescent Adult Age Factors Arizona Biopsy Blood Glucose Calpain Child Diabetes Mellitus, Type 2 Female Genotype Glucose Tolerance Test Humans Indians, North American Insulin Resistance Male Middle Aged Muscle Proteins Muscles Polymorphism, Genetic RNA, Messenger Sex Factors

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