title: The role of eight polymorphisms in three candidate genes in determining the susceptibility, phenotype, and response to anti-TNF therapy in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Several single nucleotide polymorphisms (SNPs) have been associated with rheumatoid arthritis (RA) such as peptidylarginine deiminase-4 (PADI4), osteopontin (OPN), and perforin (PRF1) genes. Thus, we aimed at analysing the influence of eight SNPs in these candidate genes on RA susceptibility and their association with laboratory and clinical features in terms of response to anti-TNF therapy.
  
  
  METHODS
  We performed a case-control study on 377 Caucasian RA patients and 391 healthy, ethnicity-matched, population-based controls. All subjects were genotyped for PADI4_89/94, PADI4_92, PADI4_104, PADI4_100 in PADI4; -156G/GG and +1239A/C in OPN and A91V and N252S in PRF1 genes. The patients were stratified for shared epitope (SE) HLA-DRB1. rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA) were analysed. The patients started anti-TNF treatment and they were evaluated at baseline and after 12 weeks. Disease activity was evaluated with DAS28 and response to treatment with EULAR criteria.
  
  
  RESULTS
  A statistically significant association between RA and OPN -156G/GG was found (p=0.023). SE was firmly confirmed to be associated with RA (OR=3.68; p<10-10). No other statistically significant association with clinical and laboratory features were observed.
  
  
  CONCLUSIONS
  For the first time, in an Italian cohort, we report the association between -156G/GG in OPN gene and RA susceptibility. Short-term response to anti-TNF therapy was not influenced by the genetic variants studied.
authors.affiliation: Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Roma, Italy. fulviaceccarelli@gmail.com
authors.forename: Fulvia
authors.initials: F
authors.lastname: Ceccarelli
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.forename: Carlo
authors.initials: C
authors.lastname: Perricone
authors.forename: Yari
authors.initials: Y
authors.lastname: Carlomagno
authors.forename: Cristiano
authors.initials: C
authors.lastname: Alessandri
authors.forename: Cristina
authors.initials: C
authors.lastname: Croia
authors.forename: Nadia
authors.initials: N
authors.lastname: Barizzone
authors.forename: Carlomaurizio
authors.initials: C
authors.lastname: Montecucco
authors.forename: Mauro
authors.initials: M
authors.lastname: Galeazzi
authors.forename: Gian Domenico
authors.initials: GD
authors.lastname: Sebastiani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Minisola
authors.forename: Ugo
authors.initials: U
authors.lastname: Fiocco
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D006867:Hydrolases / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D053495:Osteopontin / Q000235:genetics*; D010456:Peptides, Cyclic / Q000276:immunology; D054353:Perforin; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D012217:Rheumatoid Factor / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D015415:Biomarkers; D059811:HLA-DRB1 Chains; C510468:PRF1 protein, human; D010456:Peptides, Cyclic; D052899:Pore Forming Cytotoxic Proteins; C506895:SPP1 protein, human; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D053495:Osteopontin; D054353:Perforin; D012217:Rheumatoid Factor; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases