Chondroitin sulfate β-1, 4-N-acetylgalactosaminyltransferase-1 (ChGn-1) polymorphism: Association with progression of multiple sclerosis. (July 2016) - Saigoh, Kazumasa
Highlights: We found the cSNP (rs140161612) in approximately 10% of patients with multiple sclerosis (MS). The cSNP is changed from serine to leucine at position 126 (p.S126L). The expressed ChGn-1 mutant protein exhibited no N -acetylgalactosaminyl T-II activities. In male, MS patients with p.S126L had a slower disease progression than patients without it. By contrast, in female, p.S126L did not affect disease progression. Abstract: Chondroitin sulfate proteoglycans (CSPGs) are a constituent of the matrix of the central nervous system (CNS), likely participating as regulatory molecules in the process of demyelination, remyelination, axonal degeneration and regeneration in the CNS. ChGn-1 is a key enzyme for production of CSPGs and knock-out mice of this gene showed better recovery from spinal cord injury. We hypothesized that the clinical course of multiple sclerosis (MS) is influenced by the level of expression of ChGn-1 gene. We recruited 147 patients with MS and 181 healthy control subjects and analyzed single nucleotide polymorphisms (SNPs) of this gene. We found the coding SNP (cSNP: rs140161612) in approximately 10% of patients with MS as well as normal controls. The cSNP is changed from serine to leucine at position 126 (p.S126L). The expressed ChGn-1 mutant proteins exhibited no enzyme activities in COS-1 cells. In men, patients who had MS with S126L had a slower disease progression. This cSNP might be associated with the sex differences in clinical course of MS.