Evaluation of the Frequency of  (rs2227981 and rs2282055) Single Nucleotide Polymorphisms in Programmed Cell Death 1 and Its Ligand Genes of Iraqi Patients With Multiple Sclerosis

Abstract Multiple sclerosis (MS) is a central nervous system disease that causes demyelination and persistent inflammation and most of them among young adults. The current study aimed to assess gene polymorphism of PDCD1 and PDLCD1 genes and the frequency of two SNPs (rs2227981 and rs2282055). MS patients (n=100) were divided into two groups; newly diagnosed (42), and patients with ongoing treatments (58). These groups were compared to healthy subjects (n=55); the mean age ±SD was (30±8.46 years), (37±8.06years), and (31±8.73 years) for MS newly patients, patients with ongoing treatments, and healthy subjects, respectively. Studies for gene polymorphism of PDCD1 and PDLCD1 Genes and the Frequency of Two SNPs (rs2227981 and rs2282055) were measured by Real-time PCR by used HRM. The results of this study found that the genotypic frequencies of MS patient were 31% (n=31) normal AA and 48 % (n=48) heterozygous AG. Mutant homozygous was found in GG 21 % (n=21). In controls, the results demonstrate 69% (n=38) wild type AA, 27.27% (n=15) heterozygous AG and mutant homozygous GG 3.6% (n=2). The odds ratio for the GG genotype was 12.8 (0.2-5.9) with p=0.001 indicating that the homomutant genotype In PD1 gene polymorphism rs2227981 GG was a higher risk of MS than the wild-type PD1 gene polymorphism rs2227981 AA, The PD1 gene polymorphism rs2227981 AG genotype has the second risk of MS after PD1 gene polymorphism rs2227981GG with 3.92 fold high risk than the wild type AA (OR =3.92 (1.8-8.2) p=0.0003). The present study concludes that the population-based case-control study, which focused on the three PD-1 SNPs PD-1.3, PD-1.5, and PD-1.9, found that polymorphism variation might actually be a disease-modifying factor as opposed to an MS risk factor. There were substantially more PD-L1 gene SNP loci in MS patients compared to controls, and there were significantly more PD-L1 gene SNP loci in MS patients compared to controls. The pathogenesis of MS might be connected to PD-1 and PD-L1 SNPs. PD-L1 gene SNP locus rs2282055 and PD-1 gene SNP locus rs2227981 might be potential MS candidate polymorphism loci.