For example, nucleotide variation in the interleukin 7 receptor (IL7RA), the interleukin 2 receptor (IL2RA), the CD58 and the c-type lectin domain family 16 member A (CLEC16A) genes has been consistently associated with MS in several populations.
Functional investigations suggest a potential mechanism whereby increases in CD58 expression, mediated by the protective allele, up-regulate the expression of transcription factor FoxP3 through engagement of the CD58 receptor, CD2, leading to the enhanced function of CD4(+)CD25(high) regulatory T cells that are defective in subjects with MS.
In a previous genome-wide association study, cluster of differentiation 58 (CD58) region was found to be susceptible for the risk of multiple sclerosis (MS) in Caucasian, and the association between CD58 variants and MS was replicated in Americans.
In addition, they imply that concentrations of susceptibility alleles at IL2RA, IL7R, EVI5, KIAA0350, and CD58 are partly responsible for the heightened prevalence of multiple sclerosis within multiplex families.
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.
Minor (C) variant of the single-nucleotide polymorphism (SNP) rs1335532 is associated with lower MS risk according to genome-wide association studies (GWAS) and its presence correlates with higher CD58 mRNA levels in MS patients.
Of the 17 IMSGC SNPs, five SNPs showed genome-wide significant association with MS: HLA-DRA (P=8E-124), IL7R (P=6E-09), IL2RA (P=1E-11), CD58 (P=4E-09) and CLEC16A (P=3E-12).
Polymorphisms in CD48 have been linked to susceptibility to multiple sclerosis (MS), and altered expression of the structurally related protein CD58 (LFA-3) is associated with disease remission in MS. We examined CD48 expression and function in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We found that a subpopulation of CD4<sup>+</sup> T cells highly upregulated CD48 expression during EAE and were enriched for pathogenic CD4<sup>+</sup> T cells.
Recent association studies in multiple sclerosis (MS) have identified and replicated several single nucleotide polymorphism (SNP) susceptibility loci including CLEC16A, IL2RA, IL7R, RPL5, CD58, CD40 and chromosome 12q13-14 in addition to the well established allele HLA-DR15.
Single nucleotide polymorphisms (SNPs) within the first intron of CD58 have been independently confirmed to be related to the risk of MS. We here provide evidence that these SNPs may implicate an altered processing of an intronic microRNA.
The study suggests that genetic variants inGPC5, CD58 and IRF8 genes may be of clinical interest in MS as predictors of age of onset and response to therapy.