Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans.
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.
Oksenberg
Jorge R
JR
Department of Neurology, University of California at San Francisco, San Francisco, CA 94143-0435, USA. oksen@itsa.ucsf.edu
Barcellos
Lisa F
LF
Cree
Bruce A C
BA
Baranzini
Sergio E
SE
Bugawan
Teodorica L
TL
Khan
Omar
O
Lincoln
Robin R
RR
Swerdlin
Amy
A
Mignot
Emmanuel
E
Lin
Ling
L
Goodin
Douglas
D
Erlich
Henry A
HA
Schmidt
Silke
S
Thomson
Glenys
G
Reich
David E
DE
Pericak-Vance
Margaret A
MA
Haines
Jonathan L
JL
Hauser
Stephen L
SL
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
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains