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Genetic variants in IL2RA and IL7R affect multiple sclerosis disease risk and progression

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Abstract

Multiple sclerosis (MS) is a common demyelinating neurodegenerative disease with a strong genetic component. Previous studies have associated genetic variants in IL2RA and IL7R in the pathophysiology of the disease. In this study, we describe the association between IL2RA (rs2104286) and IL7R (rs6897932) in the Canadian population. Genotyping 1,978 MS patients and 830 controls failed to identify any significant association between these variants and disease risk. However, stratified analysis for family history of disease and disease course identified a trend towards association for IL2RA in patients without a family history (p = 0.05; odds ratio = 0.77) and a significant association between IL7R and patients who developed progressive MS (PrMS) (p = 0.002; odds ratio = 0.73). Although not statistically significant, the effect of IL2RA (rs2104286) in patients without a family history of MS indicates that the genetic components for familial and sporadic disease are perhaps distinct. This data suggests that the onset of sporadic disease is likely determined by a large number of variants of small effect, whereas MS in patients with a family history of disease is caused by a few deleterious variants. In addition, the significant association between PrMS and rs6897932 indicates that IL7R may not be disease-causing but a determinant of disease course. Further characterization of the effect of IL2RA and IL7R genetic variants in defined MS subtypes is warranted to evaluate the effect of these genes on specific clinical outcomes and to further elucidate the mechanisms of disease onset and progression.

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Acknowledgments

We are grateful to all individuals who generously participated in this study. We thank Kevin Atkins for data collection and extraction. This research was undertaken thanks to funding from the Canada Research Chair and Canada Excellence Research Chair programs, Vancouver Costal Heath Research Institute, and the Milan & Maureen Ilich Foundation. Collection of clinical information and DNA samples was funded by the MS Society of Canada Scientific Research Foundation as part of the CCPGSMS.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Neurology, Faculty of Medicine, University of British Columbia, Vancouver, Canada

    Anthony L. Traboulsee & A. Dessa Sadovnick

  2. Department of Medical Genetics, University of British Columbia, 5639-2215 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada

    Cecily Q. Bernales, Jay P. Ross, Joshua D. Lee, A. Dessa Sadovnick & Carles Vilariño-Güell

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  1. Anthony L. Traboulsee
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  2. Cecily Q. Bernales
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  3. Jay P. Ross
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  4. Joshua D. Lee
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  5. A. Dessa Sadovnick
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  6. Carles Vilariño-Güell
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Correspondence to Carles Vilariño-Güell.

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Traboulsee, A.L., Bernales, C.Q., Ross, J.P. et al. Genetic variants in IL2RA and IL7R affect multiple sclerosis disease risk and progression. Neurogenetics 15, 165–169 (2014). https://doi.org/10.1007/s10048-014-0403-3

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  • DOI: https://doi.org/10.1007/s10048-014-0403-3

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