SNP43 of CAPN10 and the risk of type 2 Diabetes in African-Americans: the Atherosclerosis Risk in Communities Study.
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.
Garant
Michael J
MJ
Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland, Baltimore, Maryland 21201, USA.
Kao
W H Linda
WH
Brancati
Frederick
F
Coresh
Josef
J
Rami
Tejal M
TM
Hanis
Craig L
CL
Boerwinkle
Eric
E
Shuldiner
Alan R
AR
D001161:Arteriosclerosis / Q000453:epidemiology* / Q000235:genetics; D044383:Black People / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002154:Calpain / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000097:blood; D007438:Introns; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D015995:Prevalence; D012307:Risk Factors; D012959:Socioeconomic Factors; D014280:Triglycerides / Q000097:blood; D014481:United States / Q000453:epidemiology; D001741:Black or African American
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007328:Insulin; D014280:Triglycerides; D002154:Calpain; C415197:calpain 10