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- Title
A polymorphism in the TCF7 gene, C883A, is associated with type 1 diabetes.
- Authors
Noble, Janelle A; White, Amy M; Lazzeroni, Laura C; Valdes, Ana M; Mirel, Daniel B; Reynolds, Rebecca; Grupe, Andrew; Aud, Dee; Peltz, Gary; Erlich, Henry A
- Abstract
Type 1 diabetes is an autoimmune disease with a Th1 phenotype in which insulin-producing beta-cells in the pancreas are destroyed. The T-cell-specific transcription factor TCF7 activates genes involved in immune regulation and is a candidate locus for genetic susceptibility to type 1 diabetes. A nonsynonymous single nucleotide polymorphism (SNP) (Pro to Thr) in the TCF7 gene, C883A, was examined in samples from 282 Caucasian multiplex type 1 diabetic families. HLA-DRB1 and -DQB1 genotypes were previously determined for these samples, allowing data stratification based on HLA-associated risk. The transmission disequilibrium test showed significant overtransmission of the A allele from fathers (64.1%, P < 0.007) and nonsignificant overtransmission (57.4%, P < 0.06) of the A allele to patients who do not carry the highest-risk HLA-DR3/DR4 genotype. Elliptical sib pair analysis showed significant associations of the A allele with type 1 diabetes in paternal transmissions (P < 0.03), transmissions to male children (P < 0.04), and in the non-DR3/DR4 group (P < 0.04). These data also suggest that TCF7 C883A may affect age of disease onset. Analysis of genotype data from surrounding SNPs suggests that this TCF7 polymorphism may itself represent a risk factor for type 1 diabetes.
- Publication
Diabetes, 2003, Vol 52, Issue 6, p1579
- ISSN
0012-1797
- Publication type
Journal Article
- DOI
10.2337/diabetes.52.6.1579