Association of HLA class I markers with multiple sclerosis in the Italian and UK population: evidence of two independent protective effects
| Autor: | Valeria Bargiggia, Patricia Momigliano-Richiardi, Maurizio Leone, Rosella Mechelli, Marco Salvetti, Susanna Cordera, Maria Edvige Fasano, Daniela Ferrante, Domenico Caputo, Sandra D'Alfonso, Elio Scarpini, Daniela Galimberti, Lucia Corrado, Paola Naldi, Ennia Dametto, Cristina Agliardi, Paola Cavalla, Franca Rosa Guerini, Laura Bergamaschi, Maria Ban, Francesco Monaco, Nadia Barizzone |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Linkage disequilibrium Multiple Sclerosis Population Human leukocyte antigen Biology Young Adult Gene Order Genetics Humans Genetic Predisposition to Disease Allele education Alleles Genetic Association Studies Genetics (clinical) Genetic association education.field_of_study Histocompatibility Antigens Class I HLA-DR Antigens Middle Aged United Kingdom HLA-B HLA-A Gene Expression Regulation Haplotypes Italy Case-Control Studies Immunology Cohort Female |
| Zdroj: | Journal of Medical Genetics. 48:485-492 |
| ISSN: | 1468-6244 0022-2593 |
| DOI: | 10.1136/jmg.2010.080721 |
| Popis: | Background The association of HLA A*02 with multiple sclerosis (MS) was recently confirmed by the authors, and it was observed that the combined presence of HLA Cw*05 significantly enhanced (threefold) the protective effect of HLA A*02 . Objectives and methods Since A*02 - Cw*05 is carried by two HLA extended haplotypes characterised by the B*4402 and B*1801 alleles, respectively, the association analysis was extended to HLA B*44 and B*18 in an Italian sample (1445 MS cases and 973 controls) and these associations were verified in a UK cohort (721 MS cases, 408 controls and 480 family trios). Results A strong protective effect, independent of DR15 , of the A*02 - Cw*05 combination carrying B*44 (OR 0.27, p=3.3×10 -5 ) was seen in the Italian samples and confirmed in UK family trios (OR 0.33, p=5.5×10 -4 ) and in a combined cohort of UK families and case–controls (OR 0.53, p=0.044). This protective effect was significantly stronger than that mediated by A*02 alone. Logistic regression showed that A*02 - Cw*05 maintained a significant protection when adjusted for B alleles (Italy: OR 0.38, p=6.5×10 -7 ; UK: OR 0.60, p=0.0029), indicating that it was not secondary to linkage disequilibrium with B*44 . Different from A*02 , the other HLA class I tested markers individually showed no significant ( Cw*05 , B*18) or a modest (B*44) protection when adjusted for the remaining markers. Conclusions This study identified at least two independent protective effects which are tagged by A*02–Cw*05 and A*02 , respectively. Further studies are needed to elucidate whether this protective effect is due to the presence of an unanalysed factor characterising the HLA extended haplotype(s) carrying A*02 and Cw*05 or to a direct interaction between these alleles. |
| Databáze: | OpenAIRE |
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