Single nucleotide polymorphisms in the FOXP3 gene are associated with increased risk of relapsing-remitting multiple sclerosis

Abstract

Although Multiple Sclerosis (MS) is an autoimmune multifactorial disease with unknown etiology, various genetic and environmental factors are known to contribute to the pathogenesis of the disease. Recent studies have confirmed that the suppressive function of regulatory T cells (T (reg)) is impaired in MS patients and that the FOXP3 gene is a crucial transcription factor in the regulation of CD4+CD25+FOXP3+ Treg cells. Polymorphisms in the promoter region of the FOXP3 gene may alter the gene expression level and, therefore, contribute to the disease susceptibility. The present study aimed to investigate the possible association between single nucleotide polymorphisms (SNPs) rs3761548 and rs2232365 in the FOXP3 gene and predisposition to MS. We conducted a case-control study on 410 patients with sporadic MS and 446 healthy controls. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Significant differences in distribution of both rs3761548 and rs2232365 A allele were found in MS patients in comparison to controls. Haplotype frequencies were also different among the studied groups. The A-A and C-G haplotype blocks showed a significant difference between case and controls. we have provided further evidence for the association between genetic variations and haplotypes in FOXP3 and MS in Iranian population.