title: Chondroitin sulfate β-1,4-N-acetylgalactosaminyltransferase-1 (ChGn-1) polymorphism: Association with progression of multiple sclerosis.
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.
authors.affiliation: Department of Neurology, Kinki University, Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Saigoh
authors.affiliation: Department of Neurology, Kyushu University Graduate School of Medicine, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshimura
authors.affiliation: Department of Biochemistry, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Izumikawa
authors.affiliation: Department of Biochemistry, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miyata
authors.affiliation: Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime 791-0295, Japan; Center for Genomic Medicine, Kyoto University, Graduate School of Medicine, Yoshida-honmachi, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.affiliation: Department of Neurology, Kyushu University Graduate School of Medicine, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsushita
authors.affiliation: Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Shitsukawa, Toon City, Ehime 791-0295, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.affiliation: Department of Neurology, Kinki University, Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Katsuichi
authors.initials: K
authors.lastname: Miyamoto
authors.affiliation: Department of Neurology, Kinki University, Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Makito
authors.initials: M
authors.lastname: Hirano
authors.affiliation: Department of Biochemistry, Kobe Pharmaceutical University, 4-19-1 Motoyamakitamachi, Higashinada-ku, Kobe 658-8558, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
authors.affiliation: Department of Neurology, Kyushu University Graduate School of Medicine, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kira
authors.affiliation: Department of Neurology, Kinki University, Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. Electronic address: kusunoki-tky@umin.ac.jp.
authors.forename: Susumu
authors.initials: S
authors.lastname: Kusunoki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D019556:COS Cells; D016022:Case-Control Studies; D002522:Chlorocebus aethiops; D002809:Chondroitin Sulfates / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D020125:Mutation, Missense; D017350:N-Acetylgalactosaminyltransferases / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D012737:Sex Factors; D055815:Young Adult
chemical_list: D002809:Chondroitin Sulfates; D017350:N-Acetylgalactosaminyltransferases; C472559:chondroitin sulfate N-acetylgalactosaminyltransferase-1
keywords: Demyelinating disease; Glycobiology; Glycosyltransferase; Multiple sclerosis; Proteoglycan; Sex differences