IDENTIFICATION OF A VAL-145-ILE SUBSTITUTION IN THE HUMAN MYELIN OLIGODENDROCYTE GLYCOPROTEIN - LACK OF ASSOCIATION WITH MULTIPLE-SCLEROSIS

Myelinloligodendrocyte glycoprotein (MOG) is a major target antigen in experimental autoimmune encephalomyelitis and it has been suggested t hat it may as well ploy a key role in the demyelination process in mul tiple sclerosis (MS). As MOG variants could be pathogenic in autoimmun e demyelinating diseases of the central nervous system, we analysed th e coding sequence of MOG in MS patients and described a G-->A transiti on occurring in exon 3 of the human MOG gene. The mutation predicts th at isoleucine substitutes for a valine at codon 145 (Val 145 Ile) in t he transmembrane region of the protein. This is the first aminoacid su bstitution reported in human MOG. The polymorphism con be detected by restriction enzyme digestion of genomic DNA or reverse-transcribed PCR amplified products, making it a simple tool to detect a potential imp lication of MOG alleles in susceptibility to MS by association study. The analysis of 83 unrelated MS patients and 82 unrelated healthy cont rols showed that the polymorphism is found in similar proportions in M S patients (18%) and controls (14.6%). It is therefore unlikely that t he MOG Val 145 lie variant is responsible for genetic susceptibility t o MS.