Polymorphisms and functional haplotype in PADI4: further evidence for contribution on rheumatoid arthritis susceptibility and anti-cyclic citrullinated peptide antibodies in a western Mexican population

Immunol Lett. 2015 Feb;163(2):214-20. doi: 10.1016/j.imlet.2014.10.029. Epub 2015 Jan 3.


Peptidyl arginine deiminase IV (PADI4) enzyme catalyzes the citrullination of proteins, which are recognized by anti-cyclic citrullinated peptide antibodies (anti-CCP) in rheumatoid arthritis (RA) patients. Here, we determined the association between PADI4 gene polymorphisms and haplotypes with RA susceptibility and clinical characteristics in a western Mexican population. The relationship of PADI4 polymorphisms with anti-CCP and PADI4 mRNA expression was also evaluated. PADI4_89, PADI4_90 and PADI4_92 polymorphisms were individually associated with RA susceptibility. The GTG haplotype was significantly associated with: RA susceptibility; disease onset at ≤ 40 years and anti-CCP antibodies. PADI4 expression was three fold higher in RA patients carrying the susceptibility haplotype (GTG) than in non-susceptibility haplotype carriers (ACC). In conclusion, polymorphisms and functional haplotype (GTG) in PADI4 are associated with RA susceptibility as well as anti-CCP antibodies in a Mexican population. This supports the role of PADI4 early in RA pathogenesis by promoting the generation of citrullinated autoantigens.

Keywords: Anti-CCP antibodies; Genetic susceptibility; Peptidylarginine deiminase type IV; Rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Haplotypes*
  • Humans
  • Hydrolases / genetics*
  • Linkage Disequilibrium
  • Male
  • Mexico
  • Middle Aged
  • Peptides, Cyclic / immunology
  • Polymorphism, Single Nucleotide*
  • Protein-Arginine Deiminase Type 4
  • Protein-Arginine Deiminases
  • Reverse Transcriptase Polymerase Chain Reaction


  • Autoantibodies
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Hydrolases
  • PADI4 protein, human
  • Protein-Arginine Deiminase Type 4
  • Protein-Arginine Deiminases