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

Genes & Immunity volume 9, pages 7–15 (2008)Cite this article

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.

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Acknowledgements

This work was supported by the Italian Foundation for Multiple Sclerosis (FISM grants 2001/R/44, 2002/R/40 and 2005/R/10); CARIPLO Foundation, Regione Piemonte (grants 2003 and 2004), Ministry of Health (ricerca finalizzata grant 2004.80), Eastern Piedmont University (grants to SD and PMR). NB was supported by a fellowship from FISM (2003/B/2). We thank Dr R Tosi and Dr S Sawcer for their critical suggestions. We are grateful to the patients and their parents.

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Authors and Affiliations

  1. Department of Medical Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Italy

    S D'Alfonso, E Bolognesi, N Barizzone, S Bocca, L Castelli, L Bergamaschi & P Momigliano-Richiardi

  2. Laboratory of Molecular Medicine and Biotechnology, Don C Gnocchi Foundation IRCCS, S Maria Nascente, Milan, Italy

    F R Guerini, C Agliardi & P Ferrante

  3. Department of Medical Sciences, Unit of Medical Statistics and Cancer Epidemiology, University of Eastern Piedmont and Ospedale Maggiore, Novara, Italy

    D Ferrante

  4. Department of Biomedical Sciences and Technology, University of Milan, Milan, Italy

    P Ferrante

  5. Department of Neurology, Ospedale Maggiore, Novara, Italy

    P Naldi & M Leone

  6. Multiple Sclerosis Unit, Don C Gnocchi Foundation ONLUS, IRCCS, Milan, Italy

    D Caputo

  7. Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy

    C Ballerini & L Massacesi

  8. Neurology and Center for Experimental Neurological Therapy (CENTERS), Universitá La Sapienza, Roma, Italy

    M Salvetti

  9. Department of Neurological Sciences, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

    D Galimberti

  10. Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy

    M Trojano

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  1. S D'Alfonso
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D'Alfonso, S., Bolognesi, E., Guerini, F. et al. A sequence variation in the MOG gene is involved in multiple sclerosis susceptibility in Italy. Genes Immun 9, 7–15 (2008). https://doi.org/10.1038/sj.gene.6364437

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