title: TNFAIP3 gene polymorphisms are associated with response to TNF blockade in psoriasis.
abstract: The tumor necrosis factor-alpha-induced protein 3 (TNFAIP3) gene has been associated with psoriasis, rheumatoid arthritis, type 1 diabetes mellitus, systemic lupus erythematosus, and celiac disease. TNFAIP3 encodes A20, a tumor necrosis factor (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 single-nucleotide polymorphisms (rs2230926 in exon 7 and rs610604 in intron 3) 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 up prospectively. Response variables were dichotomized separately in the two cohorts, yielding similar proportions of good responses. Whereas 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 (odds ratio (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.
authors: Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan 48109-5675, USA.
authors: Trilokraj
authors: T
authors: Tejasvi
authors: Philip E
authors: PE
authors: Stuart
authors: Vinod
authors: V
authors: Chandran
authors: John J
authors: JJ
authors: Voorhees
authors: Dafna D
authors: DD
authors: Gladman
authors: Proton
authors: P
authors: Rahman
authors: James T
authors: JT
authors: Elder
authors: Rajan P
authors: RP
authors: Nair
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D015331:Cohort Studies; D004268:DNA-Binding Proteins; D004351:Drug Resistance / Q000235:genetics*; D000068800:Etanercept; D005091:Exons; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007438:Introns; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D016896:Treatment Outcome; D000079424:Tumor Necrosis Factor Inhibitors; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D018124:Receptors, Tumor Necrosis Factor; D000079424:Tumor Necrosis Factor Inhibitors; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D000068800:Etanercept