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Clinical and Developmental Immunology
Volume 2013, Article ID 383681, 9 pages
http://dx.doi.org/10.1155/2013/383681
Research Article

PADI4 Haplotypes in Association with RA Mexican Patients, a New Prospect for Antigen Modulation

1Programa Internacional del ICB, Facultad de Medicina, Universidad Autónoma de Guadalajara, Guadalajara, JAL, Mexico
2Unidad de Investigación en Epidemiología Clínica, Hospital de Especialidades, Centro Médico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico
3División de Medicina Molecular del Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico
4Departamento de Medicina Interna-Reumatología del Hospital General Regional No. 110, Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico
5División de Genética, CIBO, IMSS and Instituto de Genética Humana, CUCS Universidad de Guadalajara, Guadalajara, JAL, Mexico
6División de Investigación en Salud, UMAE, Hospital de Especialidades, CMNO, IMSS and Departamento de Fisiología, CUCS, Universidad de Guadalajara, Mexico

Received 31 May 2013; Revised 5 September 2013; Accepted 23 September 2013

Academic Editor: Timothy B. Niewold

Copyright © 2013 Maria Guadalupe Zavala-Cerna et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity.