TheCYP24A1gene variant rs2762943 is associated with low serum 1,25‐dihydroxyvitamin D levels in multiple sclerosis patients

Abstract

AbstractBackground and purposeVitamin D is considered to play a role in multiple sclerosis (MS) etiopathogenesis. A polymorphism in theCYP24A1gene, rs2762943, was recently identified that was associated with an increased MS risk.CYP24A1encodes a protein involved in the catabolism of the active form of vitamin D. The immunological effects of carrying the rs2762943 risk allele were investigated, as well as its role as genetic modifier.MethodsSerum levels of 25‐hydroxyvitamin D and 1,25‐dihydroxyvitamin D (1,25(OH)2D) were measured in a cohort of 167 MS patients. In a subgroup of patients, expression levels of major histocompatibility complex class II and co‐stimulatory molecules were determined by flow cytometry, and serum levels of pro‐inflammatory (interferon gamma, granulocyte macrophage colony‐stimulating factor, C‐X‐C motif chemokine ligand 13) and anti‐inflammatory (interleukin 10) cytokines and neurofilament light chain were measured by single‐molecule array assays. The effect of the rs2762943 polymorphism on disease activity and disability measures was evaluated in 340 MS patients.ResultsCompared to non‐carriers, carriers of the rs2762943 risk allele were characterized by reduced levels of 1,25(OH)2D (p = 0.0001) and elevated levels of interferon gamma (p = 0.03) and granulocyte macrophage colony‐stimulating factor (p = 0.008), whereas no significant differences were observed for the other markers. The presence of the rs2762943 risk allele had no significant impact on disease activity and disability outcomes during follow‐up. However, risk allele carriers were younger at disease onset (p = 0.04).ConclusionsThese findings suggest that theCYP24A1rs2762943 polymorphism plays a more important role in MS susceptibility than in disease prognosis and is associated with lower 1,25(OH)2D levels and a heightened pro‐inflammatory environment in MS patients.