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

  • Guzmán-Guzmán I
  • Reyes-Castillo Z
  • Muñoz-Barrios S
 et al. 
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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.

Author-supplied keywords

  • Anti-CCP antibodies
  • Genetic susceptibility
  • Peptidylarginine deiminase type IV
  • Rheumatoid arthritis

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  • Iris Paola Guzmán-Guzmán

  • Zyanya Reyes-Castillo

  • Salvador Muñoz-Barrios

  • Yeniley Ruiz-Noa

  • Gloria Esther Martínez-Bonilla

  • Isela Parra-Rojas

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