TNFAIP3 Gene Polymorphisms Are Associated with Response to TNF Blockade in Psoriasis

The TNFAIP3 gene has been associated with psoriasis, rheumatoid arthritis, type 1 diabetes mellitus, systemic lupus erythematosus and celiac disease. TNFAIP3 encodes A20, a TNF-α-inducible zinc finger protein thought to limit NF-κB mediated immune responses. In this study we report association of re...

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Main Authors:	Tejasvi, Trilokraj, Stuart, Philip E., Chandran, Vinod, Voorhees, John J., Gladman, Dafna D., Rahman, Proton, Elder, James T., Nair, Rajan P.
Format:	Online
Language:	English
Published:	2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278539/

id	pubmed-3278539
recordtype	oai_dc
spelling	pubmed-32785392012-09-01 TNFAIP3 Gene Polymorphisms Are Associated with Response to TNF Blockade in Psoriasis Tejasvi, Trilokraj Stuart, Philip E. Chandran, Vinod Voorhees, John J. Gladman, Dafna D. Rahman, Proton Elder, James T. Nair, Rajan P. Article The TNFAIP3 gene has been associated with psoriasis, rheumatoid arthritis, type 1 diabetes mellitus, systemic lupus erythematosus and celiac disease. TNFAIP3 encodes A20, a TNF-α-inducible zinc finger protein thought to limit NF-κB mediated immune responses. In this study we report association of response of psoriasis to TNF blockers with two TNFAIP3 SNPs (rs2230926 in exon 3 and rs610604 in intron 6) and their haplotypes. Treatment response was self-evaluated using a 0–5 visual analog scale in 433 psoriasis patients who received TNF blockers. Confirmation was sought in 199 psoriasis and psoriatic arthritis patients from Toronto who were followed prospectively. Response variables were dichotomized separately in the two cohorts, yielding similar proportions of good responses. While significant associations were observed only for the Michigan cohort, fixed-effects meta-analysis retained significant association between dosage of the G allele of rs610604 and good combined response to all TNF blockers (OR = 1.50, pcorr = 0.050) and etanercept (OR = 1.64, pcorr = 0.016). The rs2230926 T–rs610604 G haplotype was similarly associated. By demonstrating an association with therapeutic response, these results provide a clinically relevant functional correlate to the recently described genetic association between psoriasis and TNFAIP3. 2011-11-24 2012-03 /pmc/articles/PMC3278539/ /pubmed/22113471 http://dx.doi.org/10.1038/jid.2011.376 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Tejasvi, Trilokraj Stuart, Philip E. Chandran, Vinod Voorhees, John J. Gladman, Dafna D. Rahman, Proton Elder, James T. Nair, Rajan P.
spellingShingle	Tejasvi, Trilokraj Stuart, Philip E. Chandran, Vinod Voorhees, John J. Gladman, Dafna D. Rahman, Proton Elder, James T. Nair, Rajan P. TNFAIP3 Gene Polymorphisms Are Associated with Response to TNF Blockade in Psoriasis
author_facet	Tejasvi, Trilokraj Stuart, Philip E. Chandran, Vinod Voorhees, John J. Gladman, Dafna D. Rahman, Proton Elder, James T. Nair, Rajan P.
author_sort	Tejasvi, Trilokraj
title	TNFAIP3 Gene Polymorphisms Are Associated with Response to TNF Blockade in Psoriasis
title_short	TNFAIP3 Gene Polymorphisms Are Associated with Response to TNF Blockade in Psoriasis
title_full	TNFAIP3 Gene Polymorphisms Are Associated with Response to TNF Blockade in Psoriasis
title_fullStr	TNFAIP3 Gene Polymorphisms Are Associated with Response to TNF Blockade in Psoriasis
title_full_unstemmed	TNFAIP3 Gene Polymorphisms Are Associated with Response to TNF Blockade in Psoriasis
title_sort	tnfaip3 gene polymorphisms are associated with response to tnf blockade in psoriasis
description	The TNFAIP3 gene has been associated with psoriasis, rheumatoid arthritis, type 1 diabetes mellitus, systemic lupus erythematosus and celiac disease. TNFAIP3 encodes A20, a TNF-α-inducible zinc finger protein thought to limit NF-κB mediated immune responses. In this study we report association of response of psoriasis to TNF blockers with two TNFAIP3 SNPs (rs2230926 in exon 3 and rs610604 in intron 6) and their haplotypes. Treatment response was self-evaluated using a 0–5 visual analog scale in 433 psoriasis patients who received TNF blockers. Confirmation was sought in 199 psoriasis and psoriatic arthritis patients from Toronto who were followed prospectively. Response variables were dichotomized separately in the two cohorts, yielding similar proportions of good responses. While significant associations were observed only for the Michigan cohort, fixed-effects meta-analysis retained significant association between dosage of the G allele of rs610604 and good combined response to all TNF blockers (OR = 1.50, pcorr = 0.050) and etanercept (OR = 1.64, pcorr = 0.016). The rs2230926 T–rs610604 G haplotype was similarly associated. By demonstrating an association with therapeutic response, these results provide a clinically relevant functional correlate to the recently described genetic association between psoriasis and TNFAIP3.
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278539/
_version_	1611505751946166272

TNFAIP3 Gene Polymorphisms Are Associated with Response to TNF Blockade in Psoriasis

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