Association of HLA class I markers with multiple sclerosis in the Italian and UK population: Evidence of two independent protective effects

Laura Bergamaschi, Maria Ban, Nadia Barizzone, Maurizio Leone, Daniela Ferrante, Maria Edvige Fasano, Franca R. Guerini, Lucia Corrado, Paola Naldi, Ennia Dametto, Cristina Agliardi, Marco Salvetti, Rosella Mechelli, Daniela Galimberti, Elio Scarpini, Paola Cavalla, Valeria Bargiggia, Domenico Caputo, Susanna Cordera, Francesco MonacoPatricia Momigliano-Richiardi, Sandra D'Alfonso

Research output: Contribution to journalArticlepeer-review

Abstract

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 caseecontrols (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*02eCw*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.

Original languageEnglish
Pages (from-to)485-492
Number of pages8
JournalJournal of Medical Genetics
Volume48
Issue number7
DOIs
Publication statusPublished - Jul 2011

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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