A Second Major Histocompatibility Complex Susceptibility Locus for Multiple Sclerosis
View/ Open
Author
Yeo, Tai Wai
Gregory, Simon G
Barcellos, Lisa F
Walton, Amie
Goris, An
Fenoglio, Chiara
Ban, Maria
Taylor, Craig J
Goodman, Reyna S
Walsh, Emily
Wolfish, Cara S
Horton, Roger
Traherne, James
Beck, Stephan
Trowsdale, John
Caillier, Stacy J
Green, Todd
Pobywajlo, Susan
Pericak-Vance, Margaret A
Haines, Jonathan L
Oksenberg, Jorge R
Hauser, Stephen L
Compston, Alastair
Rioux, John D
Sawcer, Stephen
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1002/ana.21063Metadata
Show full item recordCitation
Yeo, Tai Wai, Philip L De Jager, Simon G Gregory, Lisa F Barcellos, Amie Walton, An Goris, Chiara Fenoglio, et al. 2007. A second major histocompatibility complex susceptibility locus for multiple sclerosis. Annals of Neurology 61(3): 228-236.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 × 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737610/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:4737553
Collections
- HMS Scholarly Articles [17917]
Contact administrator regarding this item (to report mistakes or request changes)