Genetics

Multiple sclerosis (MS) is a complex neurodegenerative disease where genetic risk interacts biologically with the environment, notably through Vitamin D modulating the HLA-DRB1*15 susceptibility allele. Metabolic profiling links high levels of serine, lysine, acetone, and acetoacetate to increased MS risk, while revealing critical alterations in folate metabolism marked by statistically lower Homocysteine (Hcy) and Vitamin B12 (VitB12) alongside higher Cysteine (Cys) levels in patients, suggesting impaired methionine synthesis. Furthermore, in pediatric MS, higher Tryptophan (Trp) and indole lactate were associated with a lower MS risk, but higher levels of the pro-inflammatory metabolite kynurenine correlated with increased relapse rates. Finally, lipidomic analysis revealed a distinguishing "lipid signature" of 44 lipids in Normal-Appearing White Matter (NAWM) that differentiates Primary Progressive MS (PPMS) from Secondary Progressive MS (SPMS), with glycerophospholipid metabolism being the most significantly altered pathway.