Year: 2007
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: Variation in the major histocompatibility complex (MHC) on chromosome 6p21 is known to influence susceptibility to multiple sclerosis with the strongest effect originating from the HLA-DRB1 gene in the class II region. The possibility that other genes in the MHC independently influence susceptibility to multiple sclerosis has been suggested but remains unconfirmed. METHODS: Using a combination of microsatellite, single nucleotide polymorphism, and human leukocyte antigen (HLA) typing, we screened the MHC in trio families looking for evidence of residual association above and beyond that attributable to the established DRB1*1501 risk haplotype. We then refined this analysis by extending the genotyping of classical HLA loci into independent cases and control subjects. RESULTS: Screening confirmed the presence of residual association and suggested that this was maximal in the region of the HLA-C gene. Extending analysis of the classical loci confirmed that this residual association is partly due to allelic heterogeneity at the HLA-DRB1 locus, but also reflects an independent effect from the HLA-C gene. Specifically, the HLA-C*05 allele, or a variant in tight linkage disequilibrium with it, appears to exert a protective effect (p = 3.3 x 10(-5)). INTERPRETATION: Variation in the HLA-C gene influences susceptibility to multiple sclerosis independently of any effect attributable to the nearby HLA-DRB1 gene.
Source: Annals of Neurology
DOI: 10.1002/ana.21063
Authors: Tai Wai Yeo, Philip L. De Jager, Simon G. Gregory, Lisa F. Barcellos, Amie Walton, An Goris, Chiara Fenoglio, Maria Ban, Craig J. Taylor, Reyna S. Goodman, Emily Walsh, Cara S. Wolfish, Roger Horton, James Traherne, Stephan Beck, John Trowsdale, Stacy J. Caillier, Adrian J. Ivinson, Todd Green, Susan Pobywajlo, Eric S. Lander, Margaret A. Pericak‐Vance, Jonathan L. Haines, Mark J. Daly, Jorge R. Oksenberg, Stephen L. Hauser, Alastair Compston, David A. Hafler, John D. Rioux, Stephen Sawcer
Institutions: University of Cambridge, Addenbrooke's Hospital, Broad Institute, Brigham and Women's Hospital, Harvard University, Massachusetts Institute of Technology, Duke Medical Center, University of California, San Francisco, University of California, Berkeley, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Wellcome Sanger Institute, Massachusetts General Hospital, Vanderbilt University Medical Center, Montreal Heart Institute, Université de Montréal
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Cancer Research Institute, GlaxoSmithKline, Wellcome Trust, Cambridge Philosophical Society, Multiple Sclerosis Society, Fonds Wetenschappelijk Onderzoek, Cambridge Commonwealth Trust, Vlaamse regering, National Institutes of Health, Medical Research Council, National Institute of Neurological Disorders and Stroke
OpenAlex ID: W2149345837