Association of variant on the promoter of cluster of differentiation 74 in graves disease and graves ophthalmopathy

• Published in: Bioscience reports Vol. 40; no. 8
• Main Authors: Liu, Yu-Huei, Shen, Chiou-Yuan, Tsai, Fuu-Jen
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd 28.08.2020
• Subjects: 3T3-L1 Cells; Adipocytes - metabolism; Adipogenesis; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antigens, Differentiation, B-Lymphocyte - genetics; Antigens, Differentiation, B-Lymphocyte - metabolism; Case-Control Studies; Cell Proliferation; Databases, Genetic; Endocrinology; Female; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Genetic Association Studies; Genetic Predisposition to Disease; Graves Disease - diagnosis; Graves Disease - genetics; Graves Disease - metabolism; Graves Ophthalmopathy - diagnosis; Graves Ophthalmopathy - genetics; Graves Ophthalmopathy - metabolism; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - metabolism; Humans; Immunology & Inflammation; Intramolecular Oxidoreductases - genetics; Intramolecular Oxidoreductases - metabolism; Macrophage Migration-Inhibitory Factors - genetics; Macrophage Migration-Inhibitory Factors - metabolism; Male; Mice; Middle Aged; Molecular Bases of Health & Disease; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Risk Assessment; Risk Factors; Young Adult; Subject Areas: Endocrinology; Cluster of differentiation 74; Graves ophthalmopathy; Graves disease; Immunology & Inflammation; single nucleotide polymorphisms; Molecular Bases of Health & Disease
• ISSN: 0144-8463; 1573-4935; 1573-4935
• DOI: 10.1042/BSR20202072

The macrophage migration inhibitory factor (MIF)/cluster of differentiation 74 (CD74) plays a role in immunological functions. The present study aims to investigate whether single-nucleotide polymorphisms (SNPs) in the MIF and CD74 are risk factors for developing Graves ophthalmopathy (GO) in patients with Graves disease (GD). A case–control study enrolled 484 patients with GD (203 with and 281 without GO) and 1000 healthy individuals. SNPs were discriminated using real-time polymerase chain reaction. Hardy–Weinberg equilibrium, as well as frequencies of allele and genotype between GD patients with and without GO, were estimated using the Chi-square test. The effects of CD74 on adipocyte proliferation and differentiation were evaluated using 3T3-L1 preadipocytes. Quantitative DNA-immunoprecipitation was used to detect the binding capacity of NR3C1 and FOXP3 to A/G oligonucleotides. The results showed that individuals carrying the GG genotype at rs2569103 in the CD74 had a decreased risk of developing GD (P=3.390 × 10−11, odds ratio (OR) = 0.021, 95% confidence interval (CI) = 0.003–0.154); however, patients with GD carrying the AG genotype at rs2569103 in the CD74 had an increased risk of developing GO (P=0.009, OR = 1.707, 95% CI = 1.168–2.495). The knockdown of CD74 reduced adipocyte proliferation and differentiation. NR3C1 had a higher affinity for A, whereas FOXP3 had a higher affinity for G of rs2569103. The results suggested the existence of a link between the genetic variation of CD74 promoter and the risk for developing GD and GO, which should be considered in clinical practice.