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

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.

• Authors: L J Baier, 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
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 106 Issue 7 Pg. R69-73 (Oct 2000) ISSN: 0021-9738 [Print] United States
• PMID: 11018080 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Muscle Proteins
• RNA, Messenger
• Calpain

Topics

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