Comprehensive Association Analysis of Candidate Genes for Generalized Vitiligo Supports XBP1, FOXP3, and TSLP

Comprehensive Association Analysis of Candidate Genes for Generalized Vitiligo Supports XBP1, FOXP3, and TSLP

Stanca A. Birlea,Ying Jin,Dorothy C. Bennett,Deborah M. Herbstman,Margaret R. Wallace,Wayne T. McCormack,E. Helen Kemp,David J. Gawkrodger,Anthony P. Weetman,Mauro Picardo,Giovanni Leone,Alain Taïeb,Thomas Jouary,Khaled Ezzedine,Nanja van Geel,Jo Lambert,Andreas Overbeck,Pamela R. Fain,Richard A. Spritz;Stanca A. Birlea;Ying Jin;Dorothy C. Bennett;Deborah M. Herbstman;Margaret R. Wallace;Wayne T. McCormack;E. Helen Kemp;David J. Gawkrodger;Anthony P. Weetman;Mauro Picardo;Giovanni Leone;Alain Taïeb;Thomas Jouary;Khaled Ezzedine;Nanja van Geel;Jo Lambert;Andreas Overbeck;Pamela R. Fain;Richard A. Spritz;
journal of investigative dermatology 2011 Vol. 131 pp. 371-381
185
spritz2011journalcomprehensive

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.

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271909
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