High-resolution melting curve analysis of polymorphisms within CD58, CD226, HLA-G genes and association with multiple sclerosis susceptibility in a subset of Iranian population: a case–control study

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with unknown etiology, which typically is manifested in early to middle adulthood. Recently, genome-wide association studies have identified susceptibility of immune-related genes to be involved in MS predisposition. The goal of the current study was to investigate the association of single nucleotide polymorphisms (SNP) with the immunologically related genes responsible for the disease, composed of CD58 (rs2300747 A>G), CD226 (rs763361 C>T), and HLA-G (rs1611715 A>C), with MS susceptibility. In this case-control study, a total of 200 patients suffering from relapsing-remitting multiple sclerosis and 200 healthy individuals were recruited. DNA was extracted from blood and then all subjects were genotyped for the polymorphism within mentioned genes by high-resolution melting (HRM) real-time PCR method. Statistical analyses were performed using SPSS software (version 20; SPSS, Chicago, IL, USA). Our finding showed that there are significant differences in genotype and allele frequencies between two groups regarding rs763361 (P = 0.035, OR 0.64, CI 95% for C allele) and rs1611715 (P = 0.038, OR 1.57, CI 95% for AA genotype) polymorphisms within CD226 and HLA-G genes, respectively. Concerning rs2300747 polymorphism on CD58 gene, no significant differences were found between cases and controls. In general, results from the current study indicate that CD226 and HLA-G, but not CD58 genetic polymorphisms are associated with increased risk of MS in Isfahan population similar to European populations. However, to elucidate how these SNPs contribute to MS pathogenesis, functional studies are needed.

Meta-analysis of FOXP3 gene rs3761548 and rs2232365 polymorphism and multiple sclerosis susceptibility

“…Unfortunately, until now, no exact etiology of this disease was found. It was widely believed that MS may be the result of the interaction between genetic and environmental factors together [17]. Similar results were also reported between HLA alleles variant and MS [19].…”

Complete sequence analysis of human toll-like receptor 3 gene in natural killer cells of multiple sclerosis patients

“…The human leukocyte antigen (HLA) region is identified as the strongest genetic susceptibility locus for MS (Hoppenbrouwers and Hintzen, 2011), with DRB1 allele being the strongest one (Lincoln et al, 2005;Lysandropoulos et al, 2017). Other non-HLA alleles suggested to be associated with MS susceptibility include IL-7 receptor alpha gene (IL7R), IL-2 receptor alpha gene (IL2R), kinesin family member 1B (KIF1B), and CD226 (Bahreini et al, 2010;Ghavimi et al, 2018;Beecham et al, 2013;Lundmark et al, 2007). Most of the genetic factors underlying susceptibility remain to be defined.…”

Gene Expression of CD226 and Its Serum Levels in Patients With Multiple Sclerosis

“…Another study also showed the association of non-synonymous exchange (Gly307Ser) in the gene for CD226 variant with SSc and Wegener's Granulomatosis (WG) also demonstrated that (Single Nucleotide Polymorphism) SNPs located at CD226 gene, such as rs727088 and rs763361, can influence CD226 mRNA levels and different variant of these allels can be protective or predispose to autoimmune diseases [30,33]. The SNPs of each person along with the gene expression of CD226 are necessary for the exact conclusion [34].…”