TY - JOUR
T1 - A sequence variation in the MOG gene is involved in multiple sclerosis susceptibility in Italy
AU - D'Alfonso, S.
AU - Bolognesi, E.
AU - Guerini, F. R.
AU - Barizzone, N.
AU - Bocca, S.
AU - Ferrante, D.
AU - Castelli, L.
AU - Bergamaschi, L.
AU - Agliardi, C.
AU - Ferrante, P.
AU - Naldi, P.
AU - Leone, M.
AU - Caputo, D.
AU - Ballerini, C.
AU - Salvetti, M.
AU - Galimberti, D.
AU - Massacesi, L.
AU - Trojano, M.
AU - Momigliano-Richiardi, P.
N1 - Funding Information:
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.
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/38549182436
U2 - 10.1038/sj.gene.6364437
DO - 10.1038/sj.gene.6364437
M3 - Article
SN - 1466-4879
VL - 9
SP - 7
EP - 15
JO - Genes and Immunity
JF - Genes and Immunity
IS - 1
ER -