SNP43 of CAPN10 and the risk of type 2 Diabetes in African-Americans: the Atherosclerosis Risk in Communities Study

Diabetes. 2002 Jan;51(1):231-7. doi: 10.2337/diabetes.51.1.231.

Abstract

Recently, an A-to-G variant in intron 3 (SNP43) of the calcium-activated neutral protease 10 gene (CAPN10) was identified as a possible type 2 diabetes susceptibility gene through positional cloning in Mexican-Americans. We conducted cross-sectional and prospective studies to evaluate the relation between SNP43 and type 2 diabetes and related traits in middle-aged African-American participants of the Atherosclerosis Risk in Communities Study, a population-based longitudinal study. At baseline, 269 prevalent diabetes cases and 1,159 nondiabetic control subjects were studied. Those with the G/G genotype were more likely to have diabetes than those with the A/G or A/A genotype (odds ratio [OR] 1.41, 95% CI 1.00-1.99, P = 0.05). In the prospective study, 166 of the control subjects developed incident diabetes over 9 years of follow-up. The incidence of diabetes for individuals with the G/G genotype did not differ significantly from those with at least one copy of the A allele (23.3 vs. 19.5 per 1,000 person years, P = 0.29). Pooling prevalent and incident diabetic cases together, individuals with the G/G genotype were approximately 40% more likely to have diabetes than those without (OR 1.38, 95% CI 1.04-1.83, P = 0.03). Because of the high frequency of the G allele (0.88), approximately 25% of the susceptibility to type 2 diabetes in African-Americans may be attributed to the G/G genotype at SNP43 of CAPN10, although most of the subjects with the G/G genotype did not develop diabetes over the 9 years of follow-up. We conclude from this large prospective study that the G allele of SNP43 of CAPN10 or another allele or gene that is in linkage disequilibrium with it increases susceptibility to type 2 diabetes in African-Americans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • African Continental Ancestry Group / genetics*
  • Arteriosclerosis / epidemiology*
  • Arteriosclerosis / genetics
  • Blood Glucose / metabolism
  • Blood Pressure
  • Calpain / genetics*
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Genetic Variation*
  • Genotype
  • Humans
  • Incidence
  • Insulin / blood
  • Introns*
  • Male
  • Middle Aged
  • Prediabetic State / blood
  • Prediabetic State / genetics
  • Prediabetic State / physiopathology
  • Prevalence
  • Risk Factors
  • Socioeconomic Factors
  • Triglycerides / blood
  • United States / epidemiology

Substances

  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Insulin
  • Triglycerides
  • Calpain
  • calpain 10