Martínez Alfonso, Orozco Gisela, Varadé Jezabel, Sánchez López Marta, Pascual Dora, Balsa Alejandro, García Antonio, de la Concha Emilio G, Fernández-Gutiérrez Benjamín, Martín Javier, Urcelay Elena
Department of Clinical Immunology, Hospital Clinico San Carlos, Madrid, Spain.
Hum Immunol. 2007 Sep;68(9):744-7. doi: 10.1016/j.humimm.2007.06.007. Epub 2007 Jul 27.
The macrophage inhibitory factor (MIF) is a cytokine that has been implicated in several inflammatory and autoimmune diseases, including rheumatoid arthritis, systemic lupus, glomerulonephritis, and multiple sclerosis. In rheumatoid arthritis (RA), results ranging from lack of association of MIF polymorphisms with RA, to involvement in either severity or susceptibility to the disease have been reported in the past. We aimed at investigating the role of this gene in RA in the Spanish population. Two well-known MIF promoter polymorphisms were tested in 606 adult RA patients and 886 healthy controls: a single nucleotide polymorphism at -173G/C and a tetranucleotide repeat (CATT)(5-8) located at -794. We found a significant association of the allele -173C with RA (p = 0.01; odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.06-1.62). The -173C risk allele, previously reported to be transmitted in excess in patients with juvenile idiopathic arthritis, was significantly more frequent in early-onset adult RA patients than in healthy controls (p = 0.003; OR = 1.57; 95% CI = 1.14-2.15), whereas late-onset patients were not significantly different to controls (p = 0.6; OR = 1.09; 95% CI = 0.77-1.55). In conclusion, the -173C allele in the MIF promoter region is associated with increased RA predisposition, mainly in early-onset patients.
巨噬细胞抑制因子（MIF）是一种细胞因子，与多种炎症和自身免疫性疾病有关，包括类风湿性关节炎、系统性红斑狼疮、肾小球肾炎和多发性硬化症。在类风湿性关节炎（RA）中，过去曾报道过MIF基因多态性与RA缺乏关联，以及与疾病严重程度或易感性相关的各种结果。我们旨在研究该基因在西班牙人群RA中的作用。在606例成年RA患者和886例健康对照中检测了两个著名的MIF启动子多态性：-173G/C处的单核苷酸多态性和位于-794处的四核苷酸重复序列（CATT）(5-8)。我们发现-173C等位基因与RA显著相关（p = 0.01；优势比[OR] = 1.31；95%置信区间[CI] = 1.06-1.62）。-173C风险等位基因先前报道在青少年特发性关节炎患者中过度传递，在早发性成年RA患者中比健康对照显著更常见（p = 0.003；OR = 1.57；95%CI = 1.14-2.15），而晚发性患者与对照无显著差异（p = 0.6；OR = 1.09；95%CI = 0.77-1.55）。总之，MIF启动子区域的-173C等位基因与RA易感性增加相关，主要在早发性患者中。
