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Title: The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the Western Mexico
Author: Torres-Carrillo, N.M.
Ruiz-Noa, Y.
Martinez-Bonilla, G.E.
Leyva-Torres, S.D.
Torres-Carrillo, N.
Palafox-Sanchez, C.A.
Navarro-Hernandez, R.E.
Rangel-Villalobos, H.
Oregon-Romero, E.
Munoz-Valle, J.F.
Issue Date: 2012
Abstract: Introduction: Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The PTPN22 gene encodes lymphoid tyrosine phosphatase LYP, a potent negative regulator of T cell activation. Polymorphic variants of this gene have previously been associated with various autoimmune disorders. The +1858C/T single-nucleotide polymorphism (SNP) (rs2476601), in the exon 14 of the PTPN22 gene has been associated with susceptibility to RA in several population. Objective: The aim of this work was to investigate whether the +1858C/T of the PTPN22 gene is associated with susceptibility to RA in Western Mexico population. Methods: A total of 309 unrelated RA patients, classified according to American College of Rheumatology (ACR) 1987 criteria, as well as 347 controls residents from Western Mexico were recruited for this study. The DNA samples were genotyped for +1858C/T PTPN22 gene SNP using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). Results: The frequency of +1858T risk allele was significantly increased in patients with RA compared with controls (p= 0.001, OR = 2.83, 95%CI = 1.50-5.32). To confirm this results we established a comparison between subjects carrying of CT. +. TT genotypes versus those carrying CC genotype, between both groups (p= 0.004, OR = 2.65, 95%CI = 1.33-5.36). Nevertheless, we not observed association of the +1858C/T PTPN22 gene SNP with clinical activity and functional disability in RA patients. Likewise, the +1858T variant in RA patients seropositive for anti-CCP antibodies, increased the risk for RA (p= 0.008, OR = 2.5, 95%CI = 1.3-5.0) when we compared with controls; however, in the group of seronegative patients, no was found significant difference (p= 0.1, OR = 2.5, 95%CI = 0.9-7.2). Conclusions: Our results support the association of the +1858T risk allele of the +1858C/T PTPN22 polymorphism with susceptibility to RA and confirm that, in combination with anti-CCP antibodies, this SNP influence the autoimmune processes towards a development of RA in Mexican population. © 2012 Elsevier B.V.
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