title: Susceptibility to type 1 diabetes is associated with ApoCIII gene haplotypes.
abstract: Type 1 diabetes is a disease of beta-cell destruction leading to insulin deficiency. Genes for type 1 diabetes have been identified; however, much of the genetic risk remains unexplained. Genetic variation within the apolipoprotein CIII (apoCIII) gene alters apoCIII levels, which are increased in type 1 diabetes and induce beta-cell apoptosis. We therefore hypothesize haplotypes within the apoCIII gene are associated with type 1 diabetes. DNA from 584 type 1 diabetic patients and 591 control subjects were genotyped for six single nucleotide polymorphisms (SNPs) in the apoCIII gene (C-641A, C-482T, T-455C, C1100T, C3175G, and T3206G). Two alleles of a haplotype block (promoter SNPs + C3175G) were associated with type 1 diabetes. The A-T-C-C allele frequency was higher in type 1 diabetes (0.19 vs. 0.16, P = 0.05), and the C-C-T-C allele was reduced in type 1 diabetes (0.60 vs. 0.65, P = 0.04). The odds ratio (OR) for A-T-C-C allele increased with 0, 1, and 2 copies (OR of 1.00, 1.24, and 1.60, respectively; P = 0.05) and decreased for the C-C-T-C allele (1.00, 0.97, and 0.73, respectively; P = 0.03). This haplotype block contains an insulin response element. Screening for this haplotype may identify at-risk individuals, and this pathway may offer a target for prevention of type 1 diabetes.
authors.affiliation: Department of Preventive Medicine and Biometrics, Box B119, University of Colorado Health Sciences Center, Denver, CO 80262, USA. john.hokanson@uchsc.edu
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Kinney
authors.forename: Suzanne
authors.initials: S
authors.lastname: Cheng
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: Adam
authors.initials: A
authors.lastname: Kretowski
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
mesh_terms: D000328:Adult; D000483:Alleles; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic
chemical_list: D053305:Apolipoprotein C-III; D001056:Apolipoproteins C