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Linkage disequilibrium analysis of chromosome 12q14–15 in multiple sclerosis: delineation of a 118-kb interval around interferon-γ (IFNG) that is involved in male versus female differential susceptibility

Genes & Immunity volume 3, pages 470–476 (2002)Cite this article

Abstract

We have recently reported the association of a polymorphic intronic CA-repeat in the interferon-gamma gene (IFNG) with gender bias in susceptibility to multiple sclerosis (MS) in a Sardinian population. This association could refer to a functional polymorphism within IFNG or could be due to linkage disequilibrium between the IFNG marker and a neighbouring susceptibility locus. Within the average reach of linkage disequilibrium, various other candidate genes are located. Among these the most striking ones are the genes coding for the cytokines interleukin-22 (IL-22) and interleukin-26 (IL-26) that constitute together with IFNG a cytokine cluster on chromosome 12q14. To determine more precisely the location of this gender-associated susceptibility locus, we have now performed a more extensive linkage disequilibrium screen of this region using nine additional microsatellite markers. This locus appeared to be confined to a 118-kb interval that is bordered by the markers D12S313 and D12S2511, in which IFNG itself remains the main candidate gene. Haplotype analysis confirmed that this MS-associated locus protects males from developing MS according to a recessive or allele-dosage model. Our results indicate that the well-documented gender differences in susceptibility to MS are at least partially caused by genetic factors in the region surrounding IFNG.

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Acknowledgements

We gratefully acknowledge the patients and their families for their cooperation. Research at QUB on the role of chromosome 12q14–15 and IFNG in gender bias in MS is supported by RRG grant 11.5 from the Northern Ireland Health and Personal Social Services (HPSS) R&D Office. AG is a research assistant of the Fund for Scientific Research Flanders (FWO-Vlaanderen) and was supported by a Du Pré Exchange Grant of the International Federation of Multiple Sclerosis Societies. We wish to thank G. Opdenakker for support and critical reading of the manuscript. KV is Allen J. McClay Lecturer at QUB, UK.

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Authors and Affiliations

  1. Rega Institute, University of Leuven, Leuven, Belgium

    A Goris & A Billiau

  2. Department of Medical Genetics, Queen's University of Belfast, Belfast, UK

    S Heggarty & C Graham

  3. Department of Neuroscience, University of Cagliari, Cagliari, Italy

    M G Marrosu

  4. Cytokine Biology and Genetics Programme, School of Pharmacy, Queen's University of Belfast, Belfast, UK

    K Vandenbroeck

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  1. A Goris
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Correspondence to K Vandenbroeck.

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Goris, A., Heggarty, S., Marrosu, M. et al. Linkage disequilibrium analysis of chromosome 12q14–15 in multiple sclerosis: delineation of a 118-kb interval around interferon-γ (IFNG) that is involved in male versus female differential susceptibility. Genes Immun 3, 470–476 (2002). https://doi.org/10.1038/sj.gene.6363913

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