A polymorphism in the TCF7 gene, C883A, is associated with type 1 diabetes

Diabetes. 2003 Jun;52(6):1579-82. doi: 10.2337/diabetes.52.6.1579.


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 types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine
  • California
  • Cytosine
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • Diabetes Mellitus, Type 1 / genetics*
  • European Continental Ancestry Group / genetics
  • Expressed Sequence Tags
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Lymphoid Enhancer-Binding Factor 1
  • Male
  • Mutation, Missense*
  • Polymorphism, Single Nucleotide*
  • T Cell Transcription Factor 1
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • T Cell Transcription Factor 1
  • TCF7 protein, human
  • Transcription Factors
  • Cytosine
  • Adenine