Confirmation of Human Endogenous Retrovirus HERV-Fc1 role in multiple sclerosis risk
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1
Immunology Department, Hospital Clínico San Carlos. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Spain
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2
Neurogenomiks Laboratory, Dept. of Neuroscience, University of the Basque Country UPV/EHU,, Spain
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3
IKERBASQUE, Basque Foundation for Science,, Spain
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4
Inst. Parasitología y Biomedicina “López Neyra”, CSIC, Spain
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5
Multiple Sclerosis Unit, Hospital Clínico San Carlos. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Spain
Background: Multiple sclerosis (MS) is a chronic demyelinating disease with an aetiology not completely ascertained, albeit the
prevailing hypothesis contemplates the triggering effect of environmental factors in genetically susceptible individuals. The
genetics of MS has undergone a spectacular advance propelled by the genome wide association studies (GWAS) recently
performed. However, this robust approach accounts only for part of the estimated genetic load, and where the so called missing
heritability lies is intriguing. Provided GWAS do not scrutinize repetitive regions of the genome, their role in MS predisposition
gains interest. Part of these repetitive sequences corresponds to human endogenous retroviruses (HERVs), which are proviral
loci inherited under a Mendelian pattern. We aimed to validate the previously reported association of HERV-Fc1 with MS
susceptibility.
Methods: The rs391745 polymorphism located upstream of the HERV-Fc1 locus in chromosome X was genotyped by TaqMan
assays in independent cohorts from Central (714 patients and 692 controls), South (880 patients and 1359 controls) and North
(368 patients and 980 controls) Spain.
Results: North and Central Spanish cohorts including non primary progressive MS patients and showing association results
without heterogeneity were combined to achieve a higher statistical power. A significant association with MS risk was evidenced
[pM-H=0.02; OR (95% CI)=1.27 (1.03-1.55)], replicating previously reported Danish and Norwegian results. Meta-analysis of all
available data yielded a strong effect [p=0.0003; OR (95% CI)=1.32 (1.32-1.53)].
Conclusion: Our work supports the association of HERV-Fc1 in MS pathogenesis, identifying a chromosome-X genetic marker
that could lay behind genetic differences in MS clinical forms.
Acknowledgements
Angel García and Carmen Martínez provided expert technical assistance. Belen de la Hera is recipient of a PhD scholarship from ‘Fondo de Investigaciones Sanitarias’ (FI11/00560), Jezabel Varade is recipient of a contract from “Ministerio de Economía y Competitividad” (PTA2011-6137-1) and Elena Urcelay works for the Fundación para la Investigación Biomédica-Hospital Clínico San Carlos.
Fondo de Investigaciones Sanitarias FEDER-FIS [PI08/1636 and PI10/1985] and Fundación Alicia Koplowitz.
Keywords:
Multiple Sclerosis,
genetic marker,
Herv-FC1,
inmunogenetics,
neuroimmunology
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Varade
J,
De La Hera
B,
Alloza
I,
Alcina
A,
Álvarez-Lafuente
R,
Vandenbroeck
K,
Matesanz
F and
Urcelay
E
(2013). Confirmation of Human Endogenous Retrovirus HERV-Fc1 role in multiple sclerosis risk.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00309
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Received:
19 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. E Urcelay, Immunology Department, Hospital Clínico San Carlos. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain, eurcelay.hcsc@salud.madrid.org