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

TitleSNP43 of CAPN10 and the risk of type 2 Diabetes in African-Americans: the Atherosclerosis Risk in Communities Study.
Publication TypeJournal Article
Year of Publication2002
AuthorsGarant MJ, Kao LWH, Brancati F, Coresh J, Rami TM, Hanis CL, Boerwinkle E, Shuldiner AR
Corporate AuthorsAtherosclerosis Risk in Communities Study
JournalDiabetes
Volume51
Issue1
Pagination231-7
Date Published2002 Jan
ISSN0012-1797
KeywordsAfrican Continental Ancestry Group, Arteriosclerosis, Blood Glucose, Blood Pressure, Calpain, Cholesterol, HDL, Cholesterol, LDL, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Genetic Variation, Genotype, Humans, Incidence, Insulin, Introns, Male, Middle Aged, Prediabetic State, Prevalence, Risk Factors, Socioeconomic Factors, Triglycerides, United States
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.

DOI10.2337/diabetes.51.1.231
Alternate JournalDiabetes
PubMed ID11756346
Grant List1R01DK53959-01 / DK / NIDDK NIH HHS / United States
DK47487 / DK / NIDDK NIH HHS / United States
K24 DK02673-01A1 / DK / NIDDK NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
T32HL077024-23 / HL / NHLBI NIH HHS / United States