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. 2017 Jan 20;12(1):e0169956.
doi: 10.1371/journal.pone.0169956. eCollection 2017.

Polymorphisms in STAT4, PTPN2, PSORS1C1 and TRAF3IP2 Genes Are Associated With the Response to TNF Inhibitors in Patients With Rheumatoid Arthritis

Free PMC article

Polymorphisms in STAT4, PTPN2, PSORS1C1 and TRAF3IP2 Genes Are Associated With the Response to TNF Inhibitors in Patients With Rheumatoid Arthritis

Paola Conigliaro et al. PLoS One. .
Free PMC article


Objective: Rheumatoid Arthritis (RA) is a progressive autoimmune disease characterized by chronic joint inflammation and structural damage. Remission or at least low disease activity (LDA) represent potentially desirable goals of RA treatment. Single nucleotide polymorphisms (SNPs) in several genes might be useful for prediction of response to therapy. We aimed at exploring 4 SNPs in candidate genes (STAT4, PTPN2, PSORS1C1 and TRAF3IP2) in order to investigate their potential role in the response to therapy with tumor necrosis factor inhibitors (TNF-i) in RA patients.

Methods: In 171 RA patients we investigated the following SNPs: rs7574865 (STAT4), rs2233945 (PSORS1C1), rs7234029 (PTPN2) and rs33980500 (TRAF3IP2). Remission, LDA, and EULAR response were registered at 6 months and 2 years after initiation of first line TNF-i [Adalimumab (ADA) and Etanercept (ETN)].

Results: STAT4 variant allele was associated with the absence of a good/moderate EULAR response at 2 years of treatment in the whole RA group and in ETN treated patients. The PTPN2 SNP was associated with no good/moderate EULAR response at 6 months in ADA treated patients. Patients carrying PSORS1C1 variant allele did not reach LDA at 6 months in both the whole RA group and ETN treated patients. TRAF3IP2 variant allele was associated with the lack of LDA and remission achievement at 6 months in all RA cohort while an association with no EULAR response at 2 years of treatment occurred only in ETN treated patients.

Conclusions: For the first time, we reported that SNPs in STAT4, PTPN2, PSORS1C1, and TRAF3IP2 are associated with response to TNF-i treatment in RA patients; however, these findings should be validated in a larger population.

Conflict of interest statement

Giuseppe Novelli serves as Editor for PLOS ONE. This does not alter the authors’ adherence to PLOS ONE Editorial policies and criteria.


Fig 1
Fig 1. Odds ratio for associations between genetic variants and response to TNF-i treatment.
(A) Associations in the whole cohort of Rheumatoid Arthritis patients at 6 months of treatment. [I] SDAI LDA (p 0.003); [II] SDAI remission (p 0.02); [III] SDAI LDA (p 0.03). (B) Associations in patients treated with Adalimumab (grey line) and Etanercept (black lines) considered separately. [I] EULAR response at 6 months of follow up (p 0.06); [II] SDAI LDA at 6 months of follow up (p 0.023,); [III] EULAR response at 2 years of follow up (p 0.02). Multivariate logistic regression analysis was used to correct the p-value for sex, csDMARDS and ACPA/RF positivity. Odds ratios (OR) with 95% CI were reported.

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The authors received no specific funding for this work.