Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis.
In order to analyze whether loci in the human leukocyte antigen (HLA) class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis (MS), we examined selected microsatellite markers in 177 Nordic sib-pair families, 222 British sib-pair families, 323 sporadic Norwegian MS patients and 386 Norwegian controls. All samples were, in addition, genotyped for the HLA-DR DQ haplotype, and the Norwegian case-control samples were also typed for HLA-A and -B loci. In the Norwegian sporadic MS patients association was seen with HLA-A, HLA-B, and with the D6S265 marker, located 100 kb centromeric to HLA-A. Associations with HLA-A and D6S265 loci were also suggested when restricting the analysis to HLA-DR15 haplotypes. In the sib-pair data a similar trend was seen with marker D6S265. Higher genotypic relative risk (GRR) was found for individuals who carry both HLA-DR15 and -A3 (GRR = 15), compared to those who carry only HLA-DR15 (GRR = 7), only HLA-A3 (GRR = 3) or none of these alleles (GRR = 1). The highest risk was conferred by a combination of HLA-DR15 and -A3 (odds ratio (OR) = 5.2). These results suggest that HLA-A or a gene in linkage disequilibrium with it may contribute to the HLA class II-associated genetic susceptibility to MS.
Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway.
H F
HF
Harbo
B A
BA
Lie
S
S
Sawcer
E G
EG
Celius
K-Z
KZ
Dai
A
A
Oturai
J
J
Hillert
A R
AR
Lorentzen
M
M
Laaksonen
K-M
KM
Myhr
L P
LP
Ryder
S
S
Fredrikson
H
H
Nyland
P S
PS
Sørensen
M
M
Sandberg-Wollheim
O
O
Andersen
A
A
Svejgaard
A
A
Edland
S I
SI
Mellgren
A
A
Compston
F
F
Vartdal
A
A
Spurkland
D016022:Case-Control Studies; D005060:Europe; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D009103:Multiple Sclerosis / Q000209:etiology / Q000235:genetics*
D005819:Genetic Markers; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II