The regulatory T cell gene FOXP3 and genetic susceptibility to thyroid autoimmunity: an association analysis in Caucasian and Japanese cohorts

J Autoimmun. 2007 Jun;28(4):201-7. doi: 10.1016/j.jaut.2007.02.016. Epub 2007 Apr 5.


FOXP3 is a key gene in the development of regulatory T cells (Treg). FOXP3 expression commits naïve T cells to become Treg cells. Indeed, mutations in the FOXP3 gene cause severe systemic autoimmune diseases in humans and in mice. Therefore, we hypothesized that the FOXP3 gene may be associated with thyroid autoimmunity which is among the typical autoimmune diseases that develop in individuals with FOXP3 mutations. Moreover, the FOXP3 gene is located within an X-chromosome locus (Xp11.23) previously shown to be linked with autoimmune thyroid diseases (AITD). We tested the FOXP3 gene locus for association with AITD in two large cohorts of US Caucasians and Japanese AITD patients. We analyzed 269 Caucasian AITD patients (52 males and 217 females) and 357 Caucasian controls (159 males and 198 females), as well as 377 female Japanese AITD patients and 179 female Japanese controls. The FOXP3 gene locus was analyzed using four microsatellite polymorphisms [(GT)n; (TC)n; DXS573; DXS1208] flanking the FOXP3 gene locus. Interestingly, while no association was found between FOXP3 polymorphisms and AITD in the Japanese cohort there was a significant association in the Caucasian cohort. There was a significant association of the (TC)n polymorphism with AITD in the Caucasian male AITD patients (p=0.011; 5 degrees of freedom [df]). Similarly, there was an association between the DXS573 microsatellite and AITD in the Caucasian female AITD patients (p=0.00023; 4 df). These results suggest that polymorphisms of the FOXP3 gene may play a role in the genetic susceptibility to AITD in Caucasians, perhaps by altering FOXP3 function and/or expression.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asian Continental Ancestry Group*
  • Chromosomes, Human, X / genetics
  • Chromosomes, Human, X / immunology
  • Cohort Studies
  • European Continental Ancestry Group*
  • Female
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / immunology
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Mice
  • Microsatellite Repeats
  • Polymorphism, Genetic / immunology
  • Quantitative Trait Loci / immunology
  • Sex Factors
  • T-Lymphocytes, Regulatory* / immunology
  • T-Lymphocytes, Regulatory* / pathology
  • Thyroiditis, Autoimmune / ethnology
  • Thyroiditis, Autoimmune / genetics*
  • Thyroiditis, Autoimmune / immunology
  • Thyroiditis, Autoimmune / pathology


  • FOXP3 protein, human
  • Forkhead Transcription Factors