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Linkage disequilibrium between the MBP tetranucleotide repeat and multiple sclerosis is restricted to a geographically defined subpopulation in Finland

Genes & Immunity volume 4, pages 138–146 (2003)Cite this article

Abstract

We have previously found evidence for linkage as well as allelic and haplotype association between the myelin basic protein (MBP) gene and multiple sclerosis (MS). These findings have, however, not been reproduced in other populations. Here, we have analyzed association between MBP and MS in a new set of 349 Finnish triad families. Families with a parent born in the Southern Ostrobothnian region in western Finland (Bothnia families, n=98) were analyzed as a separate group since our previous studies included a high proportion of patients and families from this high-incidence region. Other families (n=251) were collected at five hospitals in southern, eastern, and northern Finland. The MBP short tandem repeat was genotyped, and haplotype patterns were verified by sequencing. In the Bothnia families, the previously detected associations with the 1.27 kb allele and haplotype 1.27-B10 were confirmed (P=0.01 and 0.02, respectively), whereas in the other families there was not even a trend toward association. These results demonstrate a geographic/genealogical restriction in the association between MS and the MBP short tandem repeat, highlight the importance of genealogical information in genetic studies of complex traits, and may provide an explanation why the association has not been found in many other populations.

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Acknowledgements

We are indebted to the patients and their families for participation in the study. Ms Seija Ahlbäck is acknowledged for her efforts in recruiting Bothnia families for this study, Ms Minna Virta and Ms Lilja Erola for excellent technical assistance. This study was financially supported by grants from the Finnish Academy (PJT), The Center of Excellence for Disease Genetics of the Academy of Finland (LP), the Multiple Sclerosis Foundation of US (LP), the Sigrid Juselius Foundation (PJT), the Helsinki University Central Hospital, and the Finnish Cultural Foundation (PJT).

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Authors and Affiliations

  1. Department of Neurology, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 4, Helsinki, Finland

    H Pihlaja, T Rantamäki, J Wikström & P J Tienari

  2. School of Public Health, University of Tampere, Finland

    M-L Sumelahti

  3. Department of Virology University of Turku, and Department of Neurology, Turku Immunology Centre, Turku University Hospital, Turku, Finland

    M Laaksonen & J Ilonen

  4. Masku Neurological Rehabilitation Centre, Masku, Finland

    J Ruutiainen

  5. Department of Neurology and Neuroscience, University of Kuopio and Kuopio University Hospital, Kuopio, Finland

    T Pirttilä

  6. Department of Neurology, University of Tampere and Tampere University Hospital, Tampere, Finland

    I Elovaara

  7. Department Neurology, University of Oulu and Oulu University Hospital, Oulu, Finland

    M Reunanen

  8. Department of Molecular Medicine, National Public Health Institute, Finland

    S Kuokkanen & L Peltonen

  9. Department of Human Genetics, UCLA School of Medicine, Los Angeles, CA, USA

    L Peltonen

  10. Central Hospital of Seinäjoki, Seinäjoki, Finland

    K Koivisto

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  1. H Pihlaja
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Correspondence to P J Tienari.

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Pihlaja, H., Rantamäki, T., Wikström, J. et al. Linkage disequilibrium between the MBP tetranucleotide repeat and multiple sclerosis is restricted to a geographically defined subpopulation in Finland. Genes Immun 4, 138–146 (2003). https://doi.org/10.1038/sj.gene.6363943

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