Comprehensive Association Analysis of Candidate Genes for Generalized Vitiligo Supports XBP1, FOXP3, and TSLP (Journal of Investigative Dermatology)

Journal of Investigative Dermatology (2011) 131, 371–381; doi:10.1038/jid.2010.337; published online 18 November 2010

Abstract

Journal of investigate DermatologyWe 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 withCTLA4 (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.

Abbreviations:

GV, generalized vitiligo; GWAS, genome-wide association study; indel, insertion–deletion; LD, linkage disequilibrium; MHC, major histocompatibility complex; OR, odds ratio; SNP, single-nucleotide polymorphism; VNTR, variable number of tandem repeats polymorphism

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