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

J Clin Invest. 2000 Oct;106(7):R69-73. 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

  • 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


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