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巨噬细胞移动抑制因子:系统性红斑狼疮中 -794 CATT5-8 和 -173 G>C 多态性与肿瘤坏死因子-α 的关联

Macrophage migration inhibitory factor: association of -794 CATT5-8 and -173 G>C polymorphisms with TNF-α in systemic lupus erythematosus.

作者信息

De la Cruz-Mosso U, Bucala R, Palafox-Sánchez C A, Parra-Rojas I, Padilla-Gutiérrez J R, Pereira-Suárez A L, Rangel-Villalobos H, Vázquez-Villamar M, Angel-Chávez L I, Muñoz-Valle J F

机构信息

Instituto de Investigación en Ciencias Biomédicas/Programa de Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.

Department of Medicine/Section of Rheumatology, Yale University School of Medicine, New Haven, USA.

出版信息

Hum Immunol. 2014 May;75(5):433-9. doi: 10.1016/j.humimm.2014.02.014. Epub 2014 Feb 12.

Abstract

Macrophage migration inhibitory factor (MIF) is an upstream immunoregulatory cytokine associated with the pathogenesis of autoimmune inflammatory diseases. There is evidence that MIF functions in a positive feedback loop with TNF-α that could perpetuate the inflammatory process in systemic lupus erythematosus (SLE). In this case-control study we investigated whether commonly occurring functional MIF polymorphisms are associated with SLE as well as with MIF and TNF-α serum levels in a Mexican-Mestizo population. Genotyping of the -794 CATT5-8 (rs5844572) and -173 G>C (rs755622) MIF polymorphisms was performed by PCR and PCR-RFLP, respectively in 186 SLE patients and 200 healthy subjects. MIF and TNF-α serum levels were determined by ELISA. A significant increase of MIF and TNF-α levels was found in SLE patients. According to a genetic model, we found a significant association of genotypes carrying the -794 CATT7 and -173(∗)C risk alleles with susceptibility to SLE and with a significant increase of TNF-α. In conclusion, MIF gene polymorphisms are associated with SLE susceptibility and with an increase of TNF-α serum levels in a Mexican-Mestizo population.

摘要

巨噬细胞移动抑制因子(MIF)是一种与自身免疫性炎症疾病发病机制相关的上游免疫调节细胞因子。有证据表明,MIF与肿瘤坏死因子-α(TNF-α)在一个正反馈回路中发挥作用,这可能会使系统性红斑狼疮(SLE)的炎症过程持续存在。在这项病例对照研究中,我们调查了常见的功能性MIF基因多态性是否与墨西哥梅斯蒂索人群的SLE以及MIF和TNF-α血清水平相关。分别通过聚合酶链反应(PCR)和聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)对186例SLE患者和200名健康受试者进行了-794 CATT5-8(rs5844572)和-173 G>C(rs755622)MIF基因多态性的基因分型。通过酶联免疫吸附测定(ELISA)测定MIF和TNF-α血清水平。在SLE患者中发现MIF和TNF-α水平显著升高。根据遗传模型,我们发现携带-794 CATT7和-173(*)C风险等位基因的基因型与SLE易感性以及TNF-α显著升高存在显著关联。总之,在墨西哥梅斯蒂索人群中,MIF基因多态性与SLE易感性以及TNF-α血清水平升高相关。

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