title: Dual effect of a polymorphism in the macrophage migration inhibitory factor gene is associated with new-onset Graves disease in a Taiwanese Chinese population.
abstract: 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 (p<0.05). A goiter-developmental model incorporating genetic (MIF 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.
authors.affiliation: Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Huei
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan; Department of Endocrinology and Metabolism, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Ching-Chu
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chen-Ming
authors.initials: CM
authors.lastname: Yang
authors.affiliation: Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan; School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan.
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D005260:Female; D005786:Gene Expression Regulation; D006111:Graves Disease / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013624:Taiwan
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human