Abstract
Aim. Impairments in folate cycle function may play a role in the pathogenesis of multiple sclerosis (MS). Genetic variants of folate metabolism enzymes and transporters, particularly MTHFR (rs1801133, rs1801131) and RFC (rs1051266), may modulate the risk of MS development and its clinical course.
Objective. To determine the impact of variants of the MTHFR (rs1801133, rs1801131) and RFC (rs1051266) genes, as well as their combinations, on the risk, progression, and potential prediction of neurological damage in MS, with a view toward identifying new preventive therapeutic strategies.
Materials and Methods. The study included 113 MS patients and 70 healthy controls. Genotyping was performed using a polymerase chain reaction with restriction fragment length polymorphism analysis. Clinical evaluation included assessment of the Expanded Disability Status Scale (EDSS) score.
Results. The 1298C allele of MTHFR (rs1801131) was associated with an increased risk of MS, while the 1298A allele had a protective effect. Additionally, the 80A allele and 80GA genotype of RFC (rs1051266) were linked to a higher risk of MS, whereas the 80G allele and 80GG genotype exhibited a protective effect. In patients with the 80GA genotype, the EDSS score was significantly lower compared to those with the 80GG and 80AA genotypes. A combined effect of variants of the MTHFR and RFC genes was identified, modifying the risk of MS and its clinical manifestations.
Conclusions. Genetic variants of MTHFR (rs1801131) and RFC (rs1051266) impact the risk of developing and the course of MS. The combination of genotypes 1298AC+80GA was associated with an increased risk of MS, whereas 80GG, in combination with functionally favorable MTHFR variants, reduced this risk.