title: A second major histocompatibility complex susceptibility locus for multiple sclerosis.
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)).
  
  
  CONCLUSIONS
  Variation in the HLA-C gene influences susceptibility to multiple sclerosis independently of any effect attributable to the nearby HLA-DRB1 gene.
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Tai Wai
authors.initials: TW
authors.lastname: Yeo
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
authors.forename: Simon G
authors.initials: SG
authors.lastname: Gregory
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
authors.forename: Amie
authors.initials: A
authors.lastname: Walton
authors.forename: An
authors.initials: A
authors.lastname: Goris
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Maria
authors.initials: M
authors.lastname: Ban
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Taylor
authors.forename: Reyna S
authors.initials: RS
authors.lastname: Goodman
authors.forename: Emily
authors.initials: E
authors.lastname: Walsh
authors.forename: Cara S
authors.initials: CS
authors.lastname: Wolfish
authors.forename: Roger
authors.initials: R
authors.lastname: Horton
authors.forename: James
authors.initials: J
authors.lastname: Traherne
authors.forename: Stephan
authors.initials: S
authors.lastname: Beck
authors.forename: John
authors.initials: J
authors.lastname: Trowsdale
authors.forename: Stacy J
authors.initials: SJ
authors.lastname: Caillier
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Ivinson
authors.forename: Todd
authors.initials: T
authors.lastname: Green
authors.forename: Susan
authors.initials: S
authors.lastname: Pobywajlo
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.forename: Alastair
authors.initials: A
authors.lastname: Compston
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.forename: John D
authors.initials: JD
authors.lastname: Rioux
authors.forename: Stephen
authors.initials: S
authors.lastname: Sawcer
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006681:HLA-D Antigens / Q000235:genetics; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D006681:HLA-D Antigens