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TCR β polymorphisms and multiple sclerosis

Genes & Immunity volume 5, pages 337–342 (2004)Cite this article

Abstract

A total of 267 families with two or more siblings with multiple sclerosis (MS) were genotyped with 14 restriction fragment length polymorphisms at the TCR β locus. A nonparametric linkage analysis of the data showed no evidence for linkage to this locus (mlod=0.11). No significant allelic or haplotype transmissions were observed in the total sample of 565 patients. After stratification for the presence of HLA DRB1*15, an association was observed between the BV25S1*1-BV26S1*1-BV2S1*1 haplotype and MS (P=0.00089). This was not significant upon correction for multiple comparisons. It was also not significant when the haplotype frequency in affected individuals was compared to a normal control sample (P=0.77). Furthermore, the associated haplotype was followed-up in an independent sample of 97 nuclear families with a single DRB1*15-positive child with MS. The BV25S1*1-BV26S1*1-BV2S1*1 haplotype did not show significant evidence for transmission distortion but the same trend was seen (P=0.21). There were no significant associations observed in the DRB1*15-negative patients and no detectable difference was seen in the DRB1*15-positive BV25S1*1-BV26S1*1-BV2S1*1 association when comparing different subgroups based on clinical course of MS. These results show no evidence for linkage and fail to establish an association between MS susceptibility and the TCR β locus.

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Acknowledgements

Funding for the Canadian Collaborative Project on Genetic Susceptibility to MS is through the MS Society of Canada Scientific Research Foundations. The MS Society of Canada has funded studentships to David Dyment and Cristen Willer. Dr Sadovnick is a Michael Smith Foundation for Health Research Distinguished Scholar.

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Author notes

  1. Members of the Canadian Collaborative Study Group: Vancouver, British Columbia: D Paty, MD; J Oger, MD; V Devonshire, MD; S Hashimoto, MD; J Hooge, MD; L Kastrukoff, MD; T Traboulsee, MD; London, Ontario: G Rice, MD; M Kremenchutzky; Calgary, Alberta: L Metz, MD; Edmonton, Alberta: S Warren, PhD; Saskatoon, Saskatchewan: W Hader, MD; Toronto, Ontario: P O'Connor, MD; M Hohol, MD; T Gray, MD; Ottawa, Ontario: M Freedman, MD; Kingston, Ontario: R Paulseth, MD; Montreal, Quebec: Y Lapierre, MD (Montreal Neurological Institute); P Duquette, MD (Hopital Notre Dame); Quebec City, Quebec: J-P Bouchard, MD; Halifax, Nova Scotia: T Murray, MD; V Bhan, MD; C Maxner, MD; St John's, Newfoundland: W Pryse-Phillips, MD; M Stefanelli, MD.

Authors and Affiliations

  1. Wellcome Trust Center for Human Genetics, Oxford, UK

    D A Dyment, J L Steckley, K Morrison, C J Willer, M Z Cader, G C DeLuca & G C Ebers

  2. Department of Medical Genetics and Faculty of Medicine, Division of Neurology, University of British Columbia, Vancouver, Canada

    A D Sadovnick

  3. Department of Genetics, Stanford University, Palo Alto, CA, USA

    N Risch

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  1. D A Dyment
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Correspondence to G C Ebers.

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Supplementary information accompanies the paper on the Genes and Immunity's website (http://www.nature.com/gene).

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Dyment, D., Steckley, J., Morrison, K. et al. TCR β polymorphisms and multiple sclerosis. Genes Immun 5, 337–342 (2004). https://doi.org/10.1038/sj.gene.6364091

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