1. Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis.
- Author
-
Harbo, H.F., Lie, B.A., Sawcer, S., Celius, E.G., Dai, K.-Z., Oturai, A., Hillert, J., Lorentzen, Å.R., Laaksonen, M., Myhr, K.-M., Ryder, L.P., Fredrikson, S., Nyland, H., Sørensen, P.S., Sandberg-Wollheim, M., Andersen, O., Svejgaard, A., Edland, A., and Mellgren, S.I.
- Subjects
- *
MICROSATELLITE repeats , *GENETIC markers , *HLA histocompatibility antigens , *MULTIPLE sclerosis , *ANTIGENS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF