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IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis

Genes & Immunity volume 6, pages 153–161 (2005)Cite this article

Abstract

Interferon-gamma (IFNγ) treatment is deleterious in multiple sclerosis (MS). MS occurs twice as frequently in women as in men. IFNγ expression varies by gender. We studied a population-based sample of US MS patients and ethnicity-matched controls and independent Northern Irish and Belgian hospital-based patients and controls for association with MS, stratified by gender, of an intron 1 microsatellite [I1(761)*CAn], a single nucleotide polymorphism 3′ of IFNG [3′(325)*G → A] and three flanking microsatellite markers spanning a 118 kb region around IFNG. Men carriers of the 3′(325)*A allele have increased susceptibility to MS compared to noncarriers in the USA (P=0.044; OR: 2.58, 95% CI: 0.97–8.08) and Northern Ireland (P=0.019; OR: 2.37, 95% CI: 1.10–5.13). There is a nonsignificant trend in the same direction in Belgian men (P=0.299; OR: 1.50, 95% CI: 0.71–3.26). Men carriers of I1(761)*CA13, which is in strong linkage disequilibrium with the 3′(325)*A, have increased susceptibility (P=0.050; OR: 2.22, 95% CI: 0.98–5.40), while men carriers of I1(761)*CA12 have decreased susceptibility (P=0.022; OR: 0.46, 95% CI: 0.23–0.90) to MS in the USA. Similar associations were reported in Sardinia between the I1(761)*CA12 allele and reduced risk of MS in men. Flanking markers were not associated with MS susceptibility. Polymorphisms of IFNG may contribute to differences in susceptibility to MS between men and women.

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Acknowledgements

The National Institute of Health, grant no. NS45442, and the National MS Society, grant no. 3406-A-6-02, to B Weinshenker, K Vandenbroeck and C Pelfrey have supported this study. The Northern Ireland HPSS R&D Office supported K Vandenbroeck, grant RRG11.5 RSG 1726. A Goris was a research assistant of the Fund for Scientific Research—Flanders (FWO—Flanders). The Mayo Foundation, grant no. DK 43694-01A2, and National Institutes of Health, grant no. MH-56207, supported C McMurray. The University Hospital Research Council, Leuven, Belgium, supported B Dubois.

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  1. O H Kantarci and A Goris: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Mayo Clinic and Foundation, Rochester, MN, USA

    O H Kantarci, D D Hebrink & B G Weinshenker

  2. Rega Institute for Medical Research, University of Leuven, Belgium

    A Goris & A Billiau

  3. Applied Genomics Group, School of Pharmacy, Queen's University of Belfast, Belfast, UK

    S Heggarty, S Cunningham, I Alloza & K Vandenbroeck

  4. Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, MN, USA

    E J Atkinson & M de Andrade

  5. Departments of Pharmacology, Biochemistry and Molecular Biology and Molecular Neuroscience Program, Mayo Clinic and Foundation, Rochester, MN, USA

    C T McMurray

  6. Northern Ireland Regional Molecular Genetics Laboratory, Belfast City Hospital Trust, UK

    C A Graham

  7. Department of Neurology, Royal Victoria Hospital, Belfast, UK

    S A Hawkins

  8. Department of Neurology, University of Leuven, Belgium

    B Dubois

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  1. O H Kantarci
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Kantarci, O., Goris, A., Hebrink, D. et al. IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis. Genes Immun 6, 153–161 (2005). https://doi.org/10.1038/sj.gene.6364164

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