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Susceptibility to Type 1 Diabetes Is Associated With ApoCIII Gene Haplotypes

¹ Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado
² Roche Molecular Systems, Alameda, California
³ Barbara Davis Center for Childhood Diabetes, Aurora, Colorado
⁴ Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland

Address correspondence and reprint requests to John E. Hokanson, PhD, Associate Professor, Department of Preventive Medicine and Biometrics, Box B119, University of Colorado Health Sciences Center, Denver, CO 80262. E-mail: john.hokanson{at}uchsc.edu

Abbreviations: apo, apolipoprotein; SNP, single nucleotide polymorphism

Type 1 diabetes is a disease of ß-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 ß-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.

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