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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

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, p _corr = 0.050) and etanercept (OR = 1.64, p _corr = 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.

Related collections

Most cited references 31

Record: found
Abstract: found
Article: not found

Rheumatoid arthritis association at 6q23.

Pille Harrison, Jane Worthington, I. D. Reid … (2007)

The Wellcome Trust Case Control Consortium (WTCCC) identified nine single SNPs putatively associated with rheumatoid arthritis at P = 1 x 10(-5) - 5 x 10(-7) in a genome-wide association screen. One, rs6920220, was unequivocally replicated (trend P = 1.1 x 10(-8)) in a validation study, as described here. This SNP maps to 6q23, between the genes oligodendrocyte lineage transcription factor 3 (OLIG3) and tumor necrosis factor-alpha-induced protein 3 (TNFAIP3).

0 comments Cited 124 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2.

Bernadette Eberlein, Sophie Debrus, Hélène Fournier … (2010)

Psoriasis is a multifactorial skin disease characterized by epidermal hyperproliferation and chronic inflammation, the most common form of which is psoriasis vulgaris (PsV). We present a genome-wide association analysis of 2,339,118 SNPs in 472 PsV cases and 1,146 controls from Germany, with follow-up of the 147 most significant SNPs in 2,746 PsV cases and 4,140 controls from three independent replication panels. We identified an association at TRAF3IP2 on 6q21 and genotyped two SNPs at this locus in two additional replication panels (the combined discovery and replication panels consisted of 6,487 cases and 8,037 controls; combined P = 2.36 × 10⁻¹⁰ for rs13210247 and combined P = 1.24 × 10⁻¹⁶ for rs33980500). About 15% of psoriasis cases develop psoriatic arthritis (PsA). A stratified analysis of our datasets including only PsA cases (1,922 cases compared to 8,037 controls, P = 4.57 × 10⁻¹² for rs33980500) suggested that TRAF3IP2 represents a shared susceptibility for PsV and PsA. TRAF3IP2 encodes a protein involved in IL-17 signaling and which interacts with members of the Rel/NF-κB transcription factor family.

0 comments Cited 114 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Genome-wide association analysis identifies three psoriasis susceptibility loci

Philip Stuart, Rajan Nair, Eva Ellinghaus … (2010)

To identify novel psoriasis susceptibility loci, we carried out a meta-analysis of two recent genome-wide association studies 1,2, yielding a discovery sample of 1,831 cases and 2,546 controls. 102 of the most promising loci in the discovery analysis were followed up in a three-stage replication study using 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland, and Germany. Association at a genome-wide level of significance for the combined discovery and replication samples was found for three genomic regions. One contains NOS2 (rs4795067, p = 4 × 10−11), another contains FBXL19 (rs10782001, p = 9 × 10−10), and a third contains PSMA6 and NFKBIA (rs12586317, p = 2 × 10−8). All three loci were also strongly associated with the subphenotypes of psoriatic arthritis and purely cutaneous psoriasis. Finally, we confirmed a recently identified3 association signal near RNF114.

0 comments Cited 108 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-journal-id): 0426720

Journal ID (pubmed-jr-id): 4839

Journal ID (nlm-ta): J Invest Dermatol

Title: The Journal of Investigative Dermatology

ISSN (Print): 0022-202X

ISSN (Electronic): 1523-1747

Publication date Nihms-submitted: 12 November 2011

Publication date (Electronic): 24 November 2011

Publication date (Print): March 2012

Publication date PMC-release: 1 September 2012

Volume: 132

Issue: 3

Pages: 593-600

Affiliations

[1 ]Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI

[2 ]University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada

[3 ]Memorial University, St. John’s, Newfoundland, Canada

[4 ]Ann Arbor Veterans Affairs Medical Center, Ann Arbor, MI

Author notes

Corresponding author: Rajan P. Nair, Ph.D., Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109-5675. Telephone 734-764-4535, Fax 734-615-7277, rnair@ 123456umich.edu

Article

Manuscript ID: nihpa333484

DOI: 10.1038/jid.2011.376

PMC ID: 3278539

PubMed ID: 22113471

SO-VID: b048f1a8-18be-4e37-9635-0329b45d25ef