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The following is a summary of “Effects of the MTHFR 677C>T (rs1801133) genetic variant on susceptibility and disability worsening in multiple sclerosis patients are mediated by homocysteine,” published in the September 2024 issue of Neurology by Ribeiro et al.

Researchers conducted a retrospective study investigating whether the MTHFR 677C>T variant and plasma homocysteine and folate levels are associated with MS susceptibility, disability, disability progression, and inflammatory biomarkers.

They included 163 patients with MS and 226 HCs. Patients were categorized as having mild (EDSS<3) or moderate/high (EDSS≥3) disability using the Expanded Disability Status Scale (EDSS). Disability progression was assessed using the Multiple Sclerosis Severity Score (MSSS). The MTHFR 677C>T variant was genotyped through real-time polymerase chain reaction, and plasma levels of inflammatory biomarkers were measured. Two new composite scores were proposed: the inflammatory activity index (IAI) and the MS severity index, based on various cytokines, TNF markers, EDSS, MSSS, and MS diagnosis.

The results showed that patients with MS had elevated homocysteine and folate levels compared to controls (P<0.001); homocysteine and M1, Th1, Th17, and Th2 Treg cytokines varied across the 3 groups, increasing from HC to mildly disabled patients with MS, and then to those with moderate/high disability (P<0.0001), TNF-α and its soluble receptors (sTNFR1, sTNFR2) were higher in patients with MS with an EDSS score ≥3 compared to those with EDSS<3 and HC (P<0.001). No link was found between MTHFR 677 C>T genotypes and MS susceptibility, disability, or progression (P>0.05). Age, immune activation index (IAI), and C-reactive protein (CRP) accounted for 21.8% of disability variance (all positively associated); 10.9% of disability progression variance was attributed to IAI and CRP (both positively), and 25-hydroxyvitamin D (negatively). The severity index (MS-EDSS-MSSS) was 54.4%, explained by age, IAI, homocysteine, folate, and CRP (all positively), and by adiponectin, body mass index, 25-hydroxyvitamin D (all negatively), female sex, and the MTHFR 677 TT genotype. In both patients and controls, 16.6% of homocysteine variance was explained by MTHFR 677 TT genotype and age (both positively), folate (negatively), and male sex.

They concluded that the MTHFR 677C>T variant has an indirect effect on the increase in disability in patients with MS, which also depends on factors such as age, sex, and folate status.

Source: msard-journal.com/article/S2211-0348(24)00459-0/abstract