Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.
Immunol Lett. 2012 Sep;147(1-2):41-6. doi: 10.1016/j.imlet.2012.05.007. Epub 2012 Jun 26.
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.
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.
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).
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).
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.
类风湿关节炎（RA）是一种常见的自身免疫性疾病，具有复杂的遗传背景。PTPN22 基因编码淋巴酪氨酸磷酸酶 LYP，是 T 细胞活化的有效负调节剂。该基因的多态性变体先前与各种自身免疫性疾病有关。PTPN22 基因外显子 14 中的+1858C/T 单核苷酸多态性（SNP）（rs2476601）与多个人群中的 RA 易感性相关。
本研究旨在探讨 PTPN22 基因+1858C/T 是否与墨西哥西部人群的 RA 易感性相关。
共招募了 309 名无血缘关系的 RA 患者，根据美国风湿病学会（ACR）1987 标准进行分类，并招募了来自墨西哥西部的 347 名对照者。使用 PCR-RFLP 技术对+1858C/T PTPN22 基因 SNP 进行 DNA 样本基因分型。通过酶联免疫吸附试验（ELISA）测量抗环瓜氨酸肽（抗-CCP）抗体。
与对照组相比，RA 患者的+1858T 风险等位基因频率显著升高（p=0.001，OR=2.83，95%CI=1.50-5.32）。为了证实这一结果，我们在携带 CT+TT 基因型的受试者与携带 CC 基因型的受试者之间进行了比较，两组之间存在显著差异（p=0.004，OR=2.65，95%CI=1.33-5.36）。然而，我们没有观察到 PTPN22 基因+1858C/T SNP 与 RA 患者的临床活动和功能障碍相关。同样，在抗-CCP 抗体阳性的 RA 患者中，+1858T 变异增加了 RA 的风险（p=0.008，OR=2.5，95%CI=1.3-5.0），与对照组相比；然而，在抗-CCP 抗体阴性患者中，没有发现显著差异（p=0.1，OR=2.5，95%CI=0.9-7.2）。
我们的结果支持 PTPN22 基因+1858T 风险等位基因与 RA 易感性相关，并证实该 SNP 与抗-CCP 抗体联合影响自身免疫过程，导致墨西哥人群中 RA 的发生。
