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J Autoimmun. 2005;25 Suppl:40-5. Epub 2005 Oct 19.

Genetic prediction of autoimmunity: initial oligogenic prediction of anti-islet autoimmunity amongst DR3/DR4-DQ8 relatives of patients with type 1A diabetes.

Author information

1
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 East 9th Avenue B-140, Denver, CO 80262, USA. theresa.aly@uchsc.edu

Abstract

In this study, the combined risk for expressing anti-islet autoantibodies and type 1A diabetes (T1D) was prospectively examined in 85 sampled relatives who had the high-risk HLA genotype (DR3-DQ8 DR4-DQ2). An insulin gene polymorphism, -23 HphI, and a lymphocyte tyrosine phosphatase gene polymorphism at position 1858C>T (amino acid 620 Arg to Trp), PTPN22/LYP, were analyzed. Life tables were created evaluating time to anti-islet autoantibody development and T1D. Of relatives with the high-risk HLA type followed for 3years, 9 of 43 (28.1%) with the high-risk -23 HphI polymorphism developed anti-islet autoantibodies versus two of 36 (5.6%) relatives with the lower-risk -23 HphI genotypes (p=0.048). Of relatives with the high-risk HLA type followed for 5years, eight of 32 (25.0%) with the high-risk -23 HphI polymorphism (A/A) developed T1D versus zero of 26 (0%) relatives with the lower-risk -23 HphI genotypes (A/T and T/T) (p=0.006). The PTPN22/LYP polymorphism, with genotypes C/C, C/T, and T/T, did not show a significant difference in risk by genotype. These results highlight the multiplicative risk of combined high-risk genotypes at different loci in terms of time to autoantibody and autoimmune disease development.

PMID:
16242305
DOI:
10.1016/j.jaut.2005.09.002
[Indexed for MEDLINE]

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