Abstract
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.
Highlights
Graves disease (GD), a complex autoimmune disorder that occurs more often in women, is characterized by the presence of autoantibodies and thyroid-stimulating immunoglobulins, targeting the thyroid-stimulating hormone receptor to stimulate both thyroid hormone synthesis and thyroid gland growth, and results in hyperthyroidism and its accompanying features [1,2,3]
Genes involved in the regulation of cell survival, DNA transcription, and protein synthesis have been considered risk factors for GD and Graves ophthalmopathy (GO) [10,35]
Overexpression of Cluster of differentiation 74 (CD74) plays a crucial role in preventing hyperreactivity between immature antigens and major histocompatibility complex class II as well as cell growth and survival, whereas down-regulation of CD74 is often correlated with autoimmunity and cell apoptosis [36]
Summary
Graves disease (GD), a complex autoimmune disorder that occurs more often in women, is characterized by the presence of autoantibodies and thyroid-stimulating immunoglobulins, targeting the thyroid-stimulating hormone receptor to stimulate both thyroid hormone synthesis and thyroid gland growth, and results in hyperthyroidism and its accompanying features [1,2,3]. Activation of orbital fibroblasts through proliferation and differentiation into adipocytes and myofibroblasts is thought to play a major role in the generation of the extracellular matrix. During inflammatory cell infiltration and edema, the activation augments the volume of tissues surrounding the eyes, which in turn leads to an increase in intraocular pressure [5]. The genome-wide approaches to determining the relative risks of developing GO are relatively
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
