Toll-like receptor 10 gene polymorphism and risk of multiple sclerosis among Iraqi patients

Abstract

Background: Toll-like receptors (TLRs) are a family of 10 pattern recognition receptors (TLR1–TLR10) involved in the regulation of inflammatory and immune responses besides their role in the pathogenesis of autoimmune diseases including multiple sclerosis (MS). TLR10 is the least studied TLR in MS, and data for single nucleotide polymorphisms (SNPs) of the TLR10 gene are limited. Therefore, a case–control study was performed on 85 patients with relapsing–remitting MS and 86 healthy controls (HC) to explore SNPs in the promoter region of TLR10 gene. A 927-bp region was amplified, and Sanger sequencing identified 10 SNPs with a minor allele frequency ≥ 10% (rs200395112 T/A, rs201802754 A/T, rs201228097 T/A, rs113588825 G/A, rs10004195 T/A, rs10034903 C/G, rs10012016 G/A/C, rs10012017 G/T, rs33994884 T/Deletion [Del] and rs28393318 A/G). Results: Del allele and T/Del genotype of rs33994884, as well as AG genotype of rs28393318, showed significantly lower frequencies in MS patients compared to HC. Allele and genotype frequencies of the 10 SNPs showed no significant differences between MS patients classified according to the Expanded Disability Status Scale. Haplotype analysis revealed that haplotype A-T-A-G-A-G-G-T-A showed a significantly increased frequency in MS patients compared to HC (odds ratio [OR] = 9.70; 95% confidence interval [CI] = 1.28–73.31; corrected probability [pc] = 0.03), while frequency of A-T-A-G-T-C-A-T-G haplotype was significantly decreased (OR = 0.10; 95% CI = 0.01–0.85; pc = 0.05). Conclusions: The study indicated that two SNPs may influence susceptibility to MS (rs33994884 and rs28393318), but haplotype analysis of TLR10 gene SNPs was more informative.