Comprehensive association analysis of candidate genes for generalized vitiligo supports XBP1, FOXP3, and TSLP

J Invest Dermatol. 2011 Feb;131(2):371-81. doi: 10.1038/jid.2010.337. Epub 2010 Nov 18.

Abstract

We previously carried out a genome-wide association study of generalized vitiligo (GV) in non-Hispanic whites, identifying 13 confirmed susceptibility loci. In this study, we re-analyzed the genome-wide data set (comprising 1,392 cases and 2,629 controls) to specifically test association of all 33 GV candidate genes that have previously been suggested for GV, followed by meta-analysis incorporating both current and previously published data. We detected association of three of the candidate genes tested: TSLP (rs764916, P=3.0E-04, odds ratio (OR)=1.60; meta-P for rs3806933=3.1E-03), XBP1 (rs6005863, P=3.6E-04, OR=1.17; meta-P for rs2269577=9.5E-09), and FOXP3 (rs11798415, P=5.8E-04, OR=1.19). Association of GV with CTLA4 (rs12992492, P=5.9E-05, OR=1.20; meta-P for rs231775=1.0E-04) seems to be secondary to epidemiological association with other concomitant autoimmune diseases. Within the major histocompatibility complex (MHC), at 6p21.33, association with TAP1-PSMB8 (rs3819721, P=5.2E-06) seems to derive from linkage disequilibrium with major primary signals in the MHC class I and class II regions.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Case-Control Studies
  • Cytokines / genetics*
  • DNA-Binding Proteins / genetics*
  • Forkhead Transcription Factors / genetics*
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Linkage Disequilibrium / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Regulatory Factor X Transcription Factors
  • Thymic Stromal Lymphopoietin
  • Transcription Factors / genetics*
  • Vitiligo / genetics*
  • X-Box Binding Protein 1

Substances

  • Cytokines
  • DNA-Binding Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • Thymic Stromal Lymphopoietin