title: Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans.
abstract: An underlying complex genetic susceptibility exists in multiple sclerosis (MS), and an association with the HLA-DRB1*1501-DQB1*0602 haplotype has been repeatedly demonstrated in high-risk (northern European) populations. It is unknown whether the effect is explained by the HLA-DRB1 or the HLA-DQB1 gene within the susceptibility haplotype, which are in strong linkage disequilibrium (LD). African populations are characterized by greater haplotypic diversity and distinct patterns of LD compared with northern Europeans. To better localize the HLA gene responsible for MS susceptibility, case-control and family-based association studies were performed for DRB1 and DQB1 loci in a large and well-characterized African American data set. A selective association with HLA-DRB1*15 was revealed, indicating a primary role for the DRB1 locus in MS independent of DQB1*0602. This finding is unlikely to be solely explained by admixture, since a substantial proportion of the susceptibility chromosomes from African American patients with MS displayed haplotypes consistent with an African origin.
authors.affiliation: Department of Neurology, University of California at San Francisco, San Francisco, CA 94143-0435, USA. oksen@itsa.ucsf.edu
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Barcellos
authors.forename: Bruce A C
authors.initials: BA
authors.lastname: Cree
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Baranzini
authors.forename: Teodorica L
authors.initials: TL
authors.lastname: Bugawan
authors.forename: Omar
authors.initials: O
authors.lastname: Khan
authors.forename: Robin R
authors.initials: RR
authors.lastname: Lincoln
authors.forename: Amy
authors.initials: A
authors.lastname: Swerdlin
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mignot
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.forename: Douglas
authors.initials: D
authors.lastname: Goodin
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: Silke
authors.initials: S
authors.lastname: Schmidt
authors.forename: Glenys
authors.initials: G
authors.lastname: Thomson
authors.forename: David E
authors.initials: DE
authors.lastname: Reich
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
mesh_terms: D000483:Alleles; D044383:Black People / Q000235:genetics*; D002874:Chromosome Mapping; D005190:Family; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics*; D014481:United States; D001741:Black or African American
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains