Association between FOXP3 polymorphisms and vitiligo in a Han Chinese population

Abstract

Background Vitiligo is an autoimmune chronic depigmentation disorder caused by melanocyte loss. Previous studies found that CD4+CD25+ regulatory T-cell (Treg) dysfunction was involved in the pathogenesis of vitiligo and that gene polymorphisms in forkhead box P3 (FOXP3) - a master regulator of Treg development and function - were associated with susceptibility to some autoimmune disorders. Therefore, we hypothesized that functional polymorphisms of the FOXP3 gene might be associated with vitiligo via dysregulation of Treg cells. Objectives To evaluate whether FOXP3 polymorphisms are associated with vitiligo risk. Material and methods In this hospital-based case-control study of 682 patients with vitiligo and 682 vitiligo-free age- and sex-matched controls, we genotyped three single nucleotide polymorphisms (SNPs) of the FOXP3 gene - rs2232365, rs3761548 and rs5902434 - by performing polymerase chain reaction with sequence-specific primers (PCR-SSP). Results Significantly increased vitiligo risk was associated with the rs2232365 GG [odds ratio (OR) 1·68, 95% confidence interval (CI) 1·17-2·39, P = 0·004] and rs3761548 AA (OR 1·82, 95% CI 1·10- 3·01, P = 0·033) genotypes compared with the rs2232365 AA and rs3761548 CC genotypes. On combined analysis of these three variant alleles, we found that individuals carrying 2-6 variant alleles had significantly increased vitiligo risk (OR 1·34, 95% CI 1·08-1·66). This risk was more pronounced in the following subgroups: age > 20 years, male sex, active vitiligo, nonsegmental vitiligo and other accompanying autoimmune diseases. Conclusions FOXP3 gene polymorphisms contributed to vitiligo risk in a Han Chinese population. What's already known about this topic? Previous findings have suggested that forkhead box P3 (FOXP3) is a master regulator of regulatory T cells (Tregs) for maintaining immune tolerance and abrogating autoimmune diseases. Dysfunction of Tregs is involved in the autoimmune mechanism of vitiligo. FOXP3 polymorphisms negatively affect the expression and functions of FOXP3 as well as of its target genes. What does this study add? Our study suggests an association between FOXP3 gene polymorphisms and vitiligo susceptibility. © 2013 The Authors BJD © 2013 British Association of Dermatologists.