Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis

Research output: Contribution to journalArticle

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.

Details

Authors
  • HF Harbo
  • BA Lie
  • S Sawcer
  • EG Celius
  • KZ Dai
  • A Oturai
  • J Hillert
  • AR Lorentzen
  • M Laaksonen
  • KM Myhr
  • LP Ryder
  • S Fredrikson
  • H Nyland
  • PS Sorensen
  • Magnhild Sandberg Wollheim
  • O Andersen
  • A Svejgaard
  • A Edland
  • SI Mellgren
  • A Compston
  • And 2 others
  • F Vartdal
  • A Spurkland
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • sclerosis, multiple, HLA-DR15, HLA-B7, HLA-A3, D6S265, genetic susceptibility
Original languageEnglish
Pages (from-to)237-247
JournalTissue Antigens
Volume63
Issue number3
Publication statusPublished - 2004
Publication categoryResearch
Peer-reviewedYes