A sequence variation in the MOG gene is involved in multiple sclerosis susceptibility in Italy

S. D'Alfonso, E. Bolognesi, F. R. Guerini, N. Barizzone, S. Bocca, D. Ferrante, L. Castelli, L. Bergamaschi, C. Agliardi, P. Ferrante, P. Naldi, M. Leone, D. Caputo, C. Ballerini, M. Salvetti, D. Galimberti, L. Massacesi, M. Trojano, P. Momigliano-Richiardi

Research output: Contribution to journalArticle

Abstract

Several studies suggest that the histocompatibility complex (HLA) class I region harbours genes modulating multiple sclerosis (MS) susceptibility independently from the effect of class II alleles. A candidate gene in this region is MOG, encoding the myelin oligodendrocyte glycoprotein. A significant association with the missense variation V142L (rs2857766) was previously reported in a small sample of 50 Italian MS patients. We confirmed this result in two independent Italian sample sets consisting of 878 MS patients and 890 matched controls (P=6.6 × 10-4) and 246 trio families (P=1.5 × 10-3). The comparison of genotype frequencies suggested a dominant-protective effect of L142. In the combined sample sets L142 conferred an odds ratio (OR)=0.70 (95% confidence interval (CI): 0.60-0.82) that remained similar after accounting for HLA-DRB1* 15 carrier status. The association with MOG V142L was still significant after conditioning for all DRB1 alleles (P=0.035). Eleven additional single nucleotide polymorphisms in the MOG gene (namely -1077T/C, -910T/C, -875A/G, -93T/C, S5S, Indel L22, V145I, +814C/T, +900A/G, +1024A/T, +1059C/T), two microsatellites in the MOG 5′ flanking (MOGCA) and 3′ untranslated (MOGTAAA) regions and four microsatellites in the HLA-class I region, from HLA-B to HFE, (namely MIB, D6S265, D6S1683 and D6S2239) were tested by transmission disequilibrium test in 199 trio families. None of these polymorphisms or of their haplotypic combinations showed a significant transmission distortion, in the absence of V142L. In conclusion, MOG V142L, or an untested variant in tight-linkage disequilibrium with it, is an independent MS susceptibility-modulating factor in the HLA class I region.

Original languageEnglish
Pages (from-to)7-15
Number of pages9
JournalGenes and Immunity
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 2008

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

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    D'Alfonso, S., Bolognesi, E., Guerini, F. R., Barizzone, N., Bocca, S., Ferrante, D., Castelli, L., Bergamaschi, L., Agliardi, C., Ferrante, P., Naldi, P., Leone, M., Caputo, D., Ballerini, C., Salvetti, M., Galimberti, D., Massacesi, L., Trojano, M., & Momigliano-Richiardi, P. (2008). A sequence variation in the MOG gene is involved in multiple sclerosis susceptibility in Italy. Genes and Immunity, 9(1), 7-15. https://doi.org/10.1038/sj.gene.6364437