Dual Effect of a Polymorphism in the Macrophage Migration Inhibitory Factor Gene Is Associated with New-Onset Graves Disease in a Taiwanese Chinese Population

Graves disease (GD) is an autoimmune disease. Macrophage migration inhibitory factor (MIF) is a potent cytokine that plays an important role in the regulation of immune responses. Two polymorphisms in the promoter region of MIF, rs5844572 and rs755622, are known to affect MIF expression. The purpose of this study was to investigate the relationship between polymorphisms in the MIF gene promoter and the severity of GD. A total of 677 individuals, including 481 GD patients and 196 ethnically matched healthy controls, were genotyped to identify differences in the distribution of the MIF polymorphisms rs5844572 and rs755622. Although there were no significant differences in the allele or genotype distributions among patients with different grades of goiter in GD and healthy controls, the distribution of the C allele, especially C/C genotype, of the rs755622 single nucleotide polymorphism (SNP) in MIF, may be as a risk factor for goiter initiation whereas a protector against development of severe goiter in patients with untreated GD (pMIF SNP rs755622) and environmental risk factors (gender, radioiodine treatment, thyroid gland surgery and vitiligo) significantly increased the prediction accuracy. Further studies are required to address the role of MIF polymorphisms, as well as their association with other candidate genes, in GD.

格雷夫斯病（Graves disease，GD）是一种自身免疫性疾病。巨噬细胞移动抑制因子（Macrophage migration inhibitory factor，MIF）是一种强效细胞因子，在免疫应答的调控中发挥重要作用。MIF基因启动子区域的两种多态性位点rs5844572与rs755622，已被证实可影响MIF的表达。本研究旨在探讨MIF基因启动子区多态性与格雷夫斯病病情严重程度之间的关联。本研究共纳入677名受试者，其中包括481名GD患者与196名种族匹配的健康对照者，通过基因分型检测以明确MIF基因多态性位点rs5844572与rs755622的分布差异。尽管GD患者中不同甲状腺肿分级亚组与健康对照者之间的等位基因及基因型分布均无显著差异，但MIF基因rs755622单核苷酸多态性（Single Nucleotide Polymorphism，SNP）的C等位基因，尤其是C/C基因型，可能作为甲状腺肿发生的风险因子，同时可对未治疗GD患者的重度甲状腺肿进展起到保护作用；结合MIF SNP rs755622与性别、放射性碘治疗、甲状腺手术及白癜风等环境风险因素进行联合分析时，模型的预测准确率显著提升。未来仍需开展进一步研究，以明确MIF基因多态性在GD发病中的作用，及其与其他候选基因之间的关联。