title: PTPN22 R620W genotype-phenotype correlation analysis and gene-environment interaction study in early rheumatoid arthritis: results from the ESPOIR cohort.
abstract: OBJECTIVE
  To investigate genotype-phenotype correlation and gene-environment interaction between PTPN22 R620W environmental factors such as tobacco/hormonal treatments in an inception cohort of RA patients.
  
  
  METHODS
  An intra-cohort study including 532 Caucasian RA patients genotyped for the PTPN22 rs2476601 polymorphism was performed. Anti-CCP and RF status at baseline, presence of bone erosions at 1 year, HLADR1 and/or DR4 status, demography, comorbidities, exposure to tobacco with the cumulative dose in pack-years, hormonal treatments and treatments received for RA were collected. Logistic regression was performed to estimate the ORs and multiplicative interaction with adjustment for confounding factors. Gene-environment interaction was estimated by the relative excess risk due to interaction (RERI), attributable proportion (AP) and synergy index (SI).
  
  
  RESULTS
  PTPN22 620W risk allele was associated with ACPA production [odds ratio (OR) = 2.21, 95% CI 1.4, 3.4, P < 0.0001]. Hormonal treatment exposition and smoking were found to act with a protective effect against ACPA production (OR = 0.44, 95% CI 0.3, 0.7, P = 0.001) and early bone erosion (OR = 0.56, 95% CI 0.4-0.8, P = 0.003), respectively, and independently of HLADR and PTPN22 status. No evidence for a gene-environment interaction was detected.
  
  
  CONCLUSIONS
  These data provide new insights into the pathogenesis of RA, underlying the pivotal key role of environmental factors in the typical heterogeneity of RA.
authors.affiliation: Rheumatology B Department, Cochin Hospital, Paris Descartes University, Medicine Faculty UPRES-EA 4058 APHP, France. carine.salliot@cch.aphp.fr
authors.forename: Carine
authors.initials: C
authors.lastname: Salliot
authors.forename: Karen
authors.initials: K
authors.lastname: Dawidowicz
authors.forename: Cédric
authors.initials: C
authors.lastname: Lukas
authors.forename: Mickael
authors.initials: M
authors.lastname: Guedj
authors.forename: Caroline
authors.initials: C
authors.lastname: Paccard
authors.forename: Joelle
authors.initials: J
authors.lastname: Benessiano
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.forename: Pascale
authors.initials: P
authors.lastname: Nicaise
authors.forename: Olivier
authors.initials: O
authors.lastname: Meyer
authors.forename: Phillippe
authors.initials: P
authors.lastname: Dieudé
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004777:Environment; D015914:Estrogen Replacement Therapy; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics* / Q000378:metabolism; D012217:Rheumatoid Factor / Q000097:blood; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22