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Title: 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
Author: Guzman-Guzman, I.P.
Reyes-Castillo, Z.
Munoz-Barrios, S.
Ruiz-Noa, Y.
Martinez-Bonilla, G.E.
Parra-Rojas, I.
Palafox-Sanchez, C.A.
Munoz-Valle, J.F.
Issue Date: 2015
Abstract: 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. � 2014 European Federation of Immunological Societies.
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