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

16 Citations (Scopus)

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

Fingerprint

Italy
Multiple Sclerosis
Microsatellite Repeats
Genes
Alleles
Myelin-Oligodendrocyte Glycoprotein
HLA-DRB1 Chains
HLA-B Antigens
Linkage Disequilibrium
3' Untranslated Regions
Major Histocompatibility Complex
Single Nucleotide Polymorphism
Odds Ratio
Genotype
Confidence Intervals

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

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

In: Genes and Immunity, Vol. 9, No. 1, 01.2008, p. 7-15.

Research output: Contribution to journalArticle

D'Alfonso, S, Bolognesi, E, Guerini, FR, 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, vol. 9, no. 1, pp. 7-15. https://doi.org/10.1038/sj.gene.6364437
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. / A sequence variation in the MOG gene is involved in multiple sclerosis susceptibility in Italy. In: Genes and Immunity. 2008 ; Vol. 9, No. 1. pp. 7-15.
@article{ef3aa158f9ed4b1084ba4fda99c2156f,
title = "A sequence variation in the MOG gene is involved in multiple sclerosis susceptibility in Italy",
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.",
author = "S. D'Alfonso and E. Bolognesi and Guerini, {F. R.} and N. Barizzone and S. Bocca and D. Ferrante and L. Castelli and L. Bergamaschi and C. Agliardi and P. Ferrante and P. Naldi and M. Leone and D. Caputo and C. Ballerini and M. Salvetti and D. Galimberti and L. Massacesi and M. Trojano and P. Momigliano-Richiardi",
year = "2008",
month = "1",
doi = "10.1038/sj.gene.6364437",
language = "English",
volume = "9",
pages = "7--15",
journal = "Genes and Immunity",
issn = "1466-4879",
publisher = "Nature Publishing Group",
number = "1",

}

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.

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 - http://www.scopus.com/inward/record.url?scp=38549182436&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38549182436&partnerID=8YFLogxK

U2 - 10.1038/sj.gene.6364437

DO - 10.1038/sj.gene.6364437

M3 - Article

VL - 9

SP - 7

EP - 15

JO - Genes and Immunity

JF - Genes and Immunity

SN - 1466-4879

IS - 1

ER -