title: A functional haplotype of PADI4 gene in rheumatoid arthritis: positive correlation in a French population.
abstract: OBJECTIVE
  A functional haplotype of peptidyl arginine deiminase 4 (PADI4) was associated with susceptibility to rheumatoid arthritis (RA) in Asian populations, but the results are contradictory in Europeans. We investigated (1) the association of 2 single-nucleotide polymorphisms (SNP) located in exon 2 of PADI4 with RA in another Caucasian population; and (2) the association between PADI4 and anti-citrullinated protein (anti-CCP) antibodies.
  
  
  METHODS
  DNA samples were obtained from 405 French RA patients and 275 controls. All RA patients met the revised criteria of the American College of Rheumatology. PADI4_89 163(G-->A) and PADI4_90 245(T-->C) SNP were genotyped using a PCR-RFLP method confirmed by direct sequencing. All patients and controls were genotyped for HLA-DRB1. The presence of anti-CCP antibodies was tested in 243 RA patients using an ELISA technique.
  
  
  RESULTS
  We focused on PADI4_89 163(G-->A) and PADI4_90 245(T-->C) SNP that distinguished 2 main haplotypes: AC haplotype (PADI4_89*A PADI4_90*C) and GT haplotype (PADI4_89*G PADI4_90*T), described, respectively, as "nonsusceptible" and "susceptible." A positive association between RA and presence of the GT haplotype was found in the heterozygous state (p = 0.002) and the homozygous state (RA patients 22%, controls 13%; p = 0.005). A correlation was observed between the presence but not the level of anti-CCP antibodies and the GT heterozygous (p = 0.03) and homozygous (p = 0.05) haplotypes. No correlation was found between the HLA-DRB1 shared epitope and any of the PADI4 haplotypes.
  
  
  CONCLUSIONS
  Our findings confirm those of Japanese, Korean, and Canadian studies and suggest that PADI4 may be a new susceptibility gene independent of HLA-DRB1 for RA in Caucasian populations.
authors.affiliation: Department of Rheumatology, Lille University Hospital, Lille, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Gandjbakhch
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fajardy
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ferré
authors.forename: Sylvain
authors.initials: S
authors.lastname: Dubucquoi
authors.forename: René-Marc
authors.initials: RM
authors.lastname: Flipo
authors.forename: Nadine
authors.initials: N
authors.lastname: Roger
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Solau-Gervais