Letter | Published:

Variation in interleukin 7 receptor α chain (IL7R) influences risk of multiple sclerosis

Nature Genetics 39, 1108–1113 (2007) | Download Citation

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Abstract

Multiple sclerosis is a chronic, often disabling, disease of the central nervous system affecting more than 1 in 1,000 people in most western countries. The inflammatory lesions typical of multiple sclerosis show autoimmune features and depend partly on genetic factors. Of these genetic factors, only the HLA gene complex has been repeatedly confirmed to be associated with multiple sclerosis, despite considerable efforts. Polymorphisms in a number of non-HLA genes have been reported to be associated with multiple sclerosis, but so far confirmation has been difficult. Here, we report compelling evidence that polymorphisms in IL7R, which encodes the interleukin 7 receptor α chain (IL7Rα), indeed contribute to the non-HLA genetic risk in multiple sclerosis, demonstrating a role for this pathway in the pathophysiology of this disease. In addition, we report altered expression of the genes encoding IL7Rα and its ligand, IL7, in the cerebrospinal fluid compartment of individuals with multiple sclerosis.

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Acknowledgements

We thank all the patients and volunteers who participated in this study. This study was supported by grants from the Swedish Research Council (project number 11220), the Norwegian Research Council (project numbers 1154888/40 and 148351/300), the Eastern Norwegian Regional Health Authority (project number 29300604), the Danish Multiple Sclerosis Society, the Warwara Larsen Foundation, NeuroproMiSe LSMH-CT-2005-018637, the Swedish Society of the Neurologically Disabled, the Bibbi and Nils Jensens Foundation and the Swedish Foundation for Strategic Research and Karolinska Institutet. We are grateful to the Knut and Alice Wallenberg Foundation.

Author information

Affiliations

  1. Division of Neurology, Department of Clinical Neuroscience, Karolinska Institutet at Karolinska University Hospital–Huddinge, SE-141 86 Stockholm, Sweden.

    • Frida Lundmark
    • , Ingrid Kockum
    •  & Jan Hillert

  2. Clinical Research Centre, Mutation Analysis Facility, Karolinska University Hospital, SE-141 86 Huddinge, Sweden.

    • Kristina Duvefelt

  3. Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet at Karolinska University Hospital–Solna, SE-171 76 Stockholm, Sweden.

    • Ellen Iacobaeus
    • , Ingrid Kockum
    • , Erik Wallström
    • , Mohsen Khademi
    •  & Tomas Olsson

  4. Danish Multiple Sclerosis Research Centre, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark.

    • Annette Oturai

  5. Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark.

    • Lars P Ryder

  6. Department of Molecular Medicine, National Public Health Institute, FI-00290 Helsinki, Finland.

    • Janna Saarela

  7. Institute of Immunology, University of Oslo, N-0027 Oslo, Norway.

    • Hanne F Harbo

  8. Department of Neurology, Ullevål University Hospital, N-0407 Oslo, Norway.

    • Hanne F Harbo
    •  & Elisabeth G Celius

  9. Pharmacogenomics Section, Department of Disease Biology, AstraZeneca R&D, SE-151 85 Södertälje, Sweden.

    • Hugh Salter

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Contributions

F.L., K.D., H.S. and J.H. planned, designed and managed the study. K.D. performed the genotyping; F.L. and I.K. performed the statistical analysis. J.H. and T.O. collected the Swedish patient and control groups. E.I., E.W., M.K., and T.O. collected material for and performed the expression analyses of IL7R and IL7. A.O., L.P.R., J.S., H.F.H. and E.G.C. took part in the planning of the study and contributed the non-Swedish groups of affected individuals and controls. J.H. and F.L. wrote the manuscript with assistance from all coauthors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jan Hillert.

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DOI

https://doi.org/10.1038/ng2106

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