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

D’Alfonso, Sandra; Bolognesi, Elisabetta; Guerini, Franca Rosa; Barizzone, Nadia; Bocca, S; Ferrante, Daniela; Castelli, Luca; Bergamaschi, Laura; Agliardi, Cristina; Ferrante, Pasquale; Naldi, Paola; Leone, Maurizio; Caputo, Domenico; Ballerini, Clara; Salvetti, Marco; Galimberti, Daniela; Massacesi, Luca; Trojano, María; Momigliano–Richiardi, Patricia

doi:10.1038/sj.gene.6364437

Cited by 22 publications

(26 citation statements)

References 61 publications

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“…The frequency of MOG-142L and HLA-A*02-positive individuals was significantly lower in cases than in controls, confirming the previously reported protective effect, 9,10,12,13 whereas the association with Cw*05 was not significant. To eliminate the possible confounding effect of linkage disequilibrium (LD) with HLA-DRB1*15, we performed the same analysis in DRB1*15-negative individuals.…”

Section: Resultssupporting

confidence: 85%

“…Conversely, the protective effect of MOG-142L was secondary to its high linkage disequilibrium with HLA-A*02. This excluded a direct role of the missense V142L variation in the MOG gene, a previously suggested strong MS susceptibility candidate (reviewed in D'Alfonso et al 12 ).…”

Section: Hla-class I Markers Involved In Ms Susceptibility L Bergamasmentioning

confidence: 88%

“…MS patients (82%) and controls (30%) in part overlap with those included in a previous paper 12 and were selected for inclusion on the basis of the availability of DNA and of HLA genotypes.…”

Section: Subjectsmentioning

confidence: 99%

“…In a panel of 1124 Italian MS patients and 1136 controls, we found a significant association with the missense variant V142L (rs2857766) in the gene encoding the Myelin Oligodendrocyte Glycoprotein (MOG) mapping in the HLA-class I region, telomeric to HLA-A (0.3 Mb) and HLA-C (1.6 Mb). 12 The 142L allele (MOG-142L) conferred an OR ¼ 0.70 (95% C.I ¼ 0.60-0.82) that remained similar after accounting for HLA-DRB1*15 carrier status. 12 Burfoot et al 13 showed similar data in a small Tasmanian population.…”

Section: Introductionmentioning

confidence: 96%

“…12 The 142L allele (MOG-142L) conferred an OR ¼ 0.70 (95% C.I ¼ 0.60-0.82) that remained similar after accounting for HLA-DRB1*15 carrier status. 12 Burfoot et al 13 showed similar data in a small Tasmanian population. Moreover, they reported a negative association with HLA-A*02, but they did not analyze if this variation was primarily associated or was dependent on MOG-142L.…”

Section: Introductionmentioning

confidence: 96%

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HLA-class I markers and multiple sclerosis susceptibility in the Italian population

et al. 2009

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Previous studies reported an association with multiple sclerosis (MS) of distinct HLA-class I markers, namely HLA-A*02, HLA-Cw*05 and MOG-142L. In this work, we tested the association with MS of A*02 and Cw*05 in 1273 Italian MS patients and 1075 matched controls, which were previously analyzed for MOG-142, and explored the relationship among these three markers in modulating MS risk. HLA-A*02 conferred a statistically robust MS protection (odds ratio, OR ¼ 0.61; 95% confidence intervals, CI ¼ 0.51-0.72, Po10 À9 ), which was independent of DRB1*15 and of any other DRB1* allele and remained similar after accounting for the other two analyzed class I markers. Conversely, the protective effect we previously observed for MOG-142L was secondary to its linkage disequilibrium with A*02. Cw*05 was not associated considering the whole sample, but its presence significantly enhanced the protection in the HLA-A*02-positive group, independently of DRB1: the OR conferred by A*02 in Cw*05-positive individuals (0.22, 95% CI ¼ 0.13-0.38) was significantly lower than in Cw*05-negative individuals (0.69, 95% CI ¼ 0.58-0.83) with a significant (P ¼ 4.94 Â 10 À5 ) multiplicative interaction between the two markers. In the absence of A*02, Cw*05 behaved as a risk factor, particularly in combination with DRB1*03 (OR ¼ 3.89, P ¼ 0.0006), indicating that Cw*05 might be a marker of protective or risk haplotypes, respectively.

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Section: Resultssupporting

confidence: 85%

Section: Hla-class I Markers Involved In Ms Susceptibility L Bergamasmentioning

confidence: 88%

Section: Subjectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 96%

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HLA-class I markers and multiple sclerosis susceptibility in the Italian population

et al. 2009

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Family-based transmission analysis of HLA genetic markers in Sardinian children with autistic spectrum disorders

et al. 2009

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Lack of association with the CD28/CTLA4/ICOS gene region among Norwegian multiple sclerosis patients

Lorentzen

Celius

Ekstrøm

et al. 2005

Journal of Neuroimmunology

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Chromosome region 2q33 encodes several regulators of the immune system, among these the CD28, CTLA4, and ICOS molecules. Involvement of these genes in multiple sclerosis (MS) is not yet clear. We investigated six microsatellites and three SNPs in a relatively large and clinically well characterised Norwegian MS cohort. No associations were observed for any of the markers analysed in 575 MS patients and 551 controls. Associations were neither found when stratifying the material for the HLA-DRB1*1501, DQB1*0602 haplotype, gender, age at onset, disease course nor familial aggregation. In conclusion, this study could not confirm association with the CD28/CTLA4/ICOS gene region.

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

Cited by 22 publications

References 61 publications

HLA-class I markers and multiple sclerosis susceptibility in the Italian population

HLA-class I markers and multiple sclerosis susceptibility in the Italian population

Family-based transmission analysis of HLA genetic markers in Sardinian children with autistic spectrum disorders

Lack of association with the CD28/CTLA4/ICOS gene region among Norwegian multiple sclerosis patients

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