title: Prevalence of functional haplotypes of the peptidylarginine deiminase citrullinating enzyme gene in patients with rheumatoid arthritis: no influence of the presence of anti-citrullinated peptide antibodies.
abstract: OBJECTIVE
  Citrullinated peptides produced by enzymatic deimination of arginine residues in proteins by peptidylarginine deiminases are of particular interest in the pathogenesis of rheumatoid arthritis (RA). One type of citrullinated protein - the cyclic citrullinated peptide - is the target of the anti-cyclic citrullinated peptide antibody, the most sensitive and specific autoantibody in RA. The peptidylarginine deiminase type 4 (PADI4) gene, which codes one of the PADI enzyme isotypes, has genetic variants that confer susceptibility to RA in Asian, but not in European populations.
  
  
  METHODS
  Genetic associations were examined in 214 Hungarian RA patients characterized for the presence of anti-CCP and rheumatoid factor. The patients were characterized for the existing haplotypes of the PADI4 gene (defined by the combinations of 4 exonic padi4_89: 163G/A, padi4_90: 245T/C, padi4_92: 335C/G, padi4_104: 349T/C and 2 intronic padi4_94: 17535226C/T and padi4_102: 17546809C/T variants) by the PCR-RFLP method.
  
  
  RESULTS
  None of the PADI4 haplotypes was accumulated in RA patients. One new finding was that we also did not detect the accumulation of any haplotypes either in the anti-CCP or in the RF-positive subgroups of patients.
  
  
  CONCLUSIONS
  The data presented here show that none of the naturally occurring haplotypes of the PADI4 gene conferred susceptibility to RA in an average group of Hungarian patients; this is in agreement with findings for other European populations. In addition, none of the functional PADI4 haplotypes were associated with the pathologic immune response, which was evidenced by the absence of accumulation of anti-CCP-positive subjects in the specific PADI4 haplotypes.
authors: Department of Medical Genetics and Child Development, University of Pécs, Pécs, Hungary.
authors: B
authors: B
authors: Faragó
authors: G C
authors: GC
authors: Talián
authors: A
authors: A
authors: Maász
authors: L
authors: L
authors: Magyari
authors: K
authors: K
authors: Horvatovich
authors: B
authors: B
authors: Kovács
authors: V
authors: V
authors: Cserép
authors: P
authors: P
authors: Kisfali
authors: C G
authors: CG
authors: Kiss
authors: L
authors: L
authors: Czirják
authors: B
authors: B
authors: Melegh
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D006814:Hungary; D006867:Hydrolases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D015995:Prevalence; D000076342:Protein-Arginine Deiminases; D012217:Rheumatoid Factor / Q000032:analysis; D044465:White People
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases