title: Polymorphisms in STAT4, PTPN2, PSORS1C1 and TRAF3IP2 Genes Are Associated with the Response to TNF Inhibitors in Patients with Rheumatoid Arthritis.
abstract: 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.
authors.affiliation: Clinic of Rheumatology, Allergology and Clinical Immunology, Department of "Medicina dei Sistemi", University of Rome Tor Vergata, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Conigliaro
authors.affiliation: Department of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ciccacci
authors.affiliation: Department of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Politi
authors.affiliation: Clinic of Rheumatology, Allergology and Clinical Immunology, Department of "Medicina dei Sistemi", University of Rome Tor Vergata, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Triggianese
authors.affiliation: Department of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Rufini
authors.affiliation: Clinic of Rheumatology, Allergology and Clinical Immunology, Department of "Medicina dei Sistemi", University of Rome Tor Vergata, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kroegler
authors.affiliation: Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Perricone
authors.affiliation: Department of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Latini
authors.affiliation: Department of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.affiliation: Department of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Borgiani
authors.affiliation: Clinic of Rheumatology, Allergology and Clinical Immunology, Department of "Medicina dei Sistemi", University of Rome Tor Vergata, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Perricone
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D050797:STAT4 Transcription Factor / Q000235:genetics*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C484393:PSORS1C1 protein, human; D011506:Proteins; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C414202:TRAF3IP2 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; C516649:PTPN2 protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2