Ruiz-Noa Yeniley, Padilla-Gutiérrez Jorge Ramón, Hernández-Bello Jorge, Palafox-Sánchez Claudia Azucena, Valle Yeminia, Oregón-Romero Edith, Pereira-Suárez Ana Laura, Bernard-Medina Ana Guilaisne, Muñoz-Valle José Francisco
Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, JAL, Mexico.
Servicio de Reumatología, OPD Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara, JAL, Mexico.
Int J Genomics. 2017;2017:8753498. doi: 10.1155/2017/8753498. Epub 2017 Jan 22.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by the presence of antibodies against cyclic citrullinated peptide (anti-CCP), a consequence of the breakdown of immune tolerance. The lymphoid tyrosine phosphatase (Lyp) protein has significant effects on maintenance of peripheral immune tolerance. Two polymorphic variants (-1123G>C and +1858C>T) at gene that encodes this protein have been associated with autoimmune disorders and found in strong linkage disequilibrium in Caucasian population. We evaluated whether haplotypes (-1123G>C/+1858C>T) are associated with anti-CCP antibodies, as well as susceptibility to RA in a Western Mexican population. A total of 315 RA patients and 315 control subjects (CS) were included. The polymorphisms were genotyped by PCR-RFLP and the anti-CCP antibodies were determined by ELISA. The polymorphisms were in strong linkage disequilibrium (D' = 1.00 in CS). The susceptibility haplotype CT was significantly more frequent in RA patients than in CS (OR 2.18, 95% CI 1.15-4.16, = 0.01). No association between haplotypes and anti-CCP antibodies levels was observed. In conclusion, this study confirmed that -1123G>C and +1858C>T polymorphisms are in strong linkage disequilibrium and the CT haplotype is a susceptibility marker to RA in Western Mexico. However, the haplotypes are not associated with anti-CCP antibodies.
类风湿关节炎(RA)是一种自身免疫性疾病,其特征是存在抗环瓜氨酸肽抗体(抗CCP),这是免疫耐受破坏的结果。淋巴样酪氨酸磷酸酶(Lyp)蛋白对维持外周免疫耐受具有重要作用。编码该蛋白的基因上的两个多态性变体(-1123G>C和+1858C>T)与自身免疫性疾病相关,并且在高加索人群中发现处于强连锁不平衡状态。我们评估了单倍型(-1123G>C/+1858C>T)是否与抗CCP抗体相关,以及在墨西哥西部人群中对RA的易感性。总共纳入了315例RA患者和315例对照受试者(CS)。通过PCR-RFLP对多态性进行基因分型,并通过ELISA测定抗CCP抗体。这些多态性处于强连锁不平衡状态(CS中D' = 1.00)。RA患者中易感性单倍型CT的频率显著高于CS(OR 2.18,95% CI 1.15-4.16,P = 0.01)。未观察到单倍型与抗CCP抗体水平之间的关联。总之,本研究证实-1123G>C和+1858C>T多态性处于强连锁不平衡状态,并且CT单倍型是墨西哥西部RA的易感性标志物。然而,这些单倍型与抗CCP抗体无关。