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

Tipo de publicaciónJournal Article
Año de publicación2015
AutoresGuzmán-Guzmán, IPaola, Reyes-Castillo, Z, Muñoz-Barrios, S, Ruiz-Noa, Y, Martínez-Bonilla, GEsther, Parra-Rojas, I, Palafox-Sánchez, CA, Muñoz-Valle, JFrancisco
JournalImmunol Lett
Fecha de publicación2015 Feb
Palabras claveAdult, Aged, Alleles, Arthritis, Rheumatoid, Autoantibodies, Female, Gene Expression Regulation, Enzymologic, Gene Frequency, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Hydrolases, Linkage Disequilibrium, Male, Mexico, Middle Aged, Peptides, Cyclic, Polymorphism, Single Nucleotide, Reverse Transcriptase Polymerase Chain Reaction

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.

Alternate JournalImmunol. Lett.
ID de PubMed25562673