Human Endogenous Retrovirus HERV-Fc1 Association with Multiple Sclerosis Susceptibility: A Meta-Analysis

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Abstract

Background

Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts.

Methods

A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data.

Results

Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: p _M-H = 0.0005; OR _M-H (95% CI) = 1.27 (1.11–1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [p _M-H = 0.0003, OR _M-H (95% CI) = 1.32 (1.14–1.53)].

Conclusion

Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.

Related collections

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Author and article information

Contributors

Fernando de Castro: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2014

Publication date (Electronic): 3 March 2014

Volume: 9

Issue: 3

Electronic Location Identifier: e90182

Affiliations

[1 ]Immunology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain

[2 ]Multiple Sclerosis Unit, Neurology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain

[3 ]Instituto de Parasitología y Biomedicina “López Neyra”, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain

[4 ]Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Leioa, Spain

[5 ]Laboratorio de Investigación, Instituto de Neurociencias Clínicas, Hospital Regional Universitario, Málaga, Spain

[6 ]Servicio de Neurología, Instituto de Neurociencias Clínicas, Hospital Regional Universitario, Málaga, Spain

[7 ]Unidad de Esclerosis Múltiple, Hospital Virgen Macarena, Sevilla, Spain

[8 ]Servicio de Neurología, Hospital de Basurto, Bilbao, Spain

[9 ]Achucarro Basque Center for Neuroscience – UPV/EHU, Zamudio, Spain

[10 ]IKERBASQUE, Basque Foundation for Science, Bilbao, Spain

Hospital Nacional de Parapléjicos – SESCAM, Spain

Author notes

* E-mail: elena.urcelay@ 123456salud.madrid.org

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: KV FM EU. Performed the experiments: BDLH JV MGM MF IA. Analyzed the data: AA IA LL RAL. Contributed reagents/materials/analysis tools: OF GI AA RA. Wrote the paper: KV FM EU.

Article

Publisher ID: PONE-D-13-44698

DOI: 10.1371/journal.pone.0090182

PMC ID: 3971560

PubMed ID: 24594754

SO-VID: 01a323dc-dc68-4802-9488-11f9d2f94eeb

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 30 October 2013

Date accepted : 27 January 2014

Page count

Pages: 6

Funding

Belén de la Hera is recipient of a PhD scholarship from “Fondo de Investigaciones Sanitarias” (FI11/00560), Jezabel Varadé benefits from a contract of “Ministerio de Economía y Competitividad” (PTA2011-6137-1) and Elena Urcelay Works for the Fundación para la Investigación Biomédica-Hospital Clínico San Carlos. This is a collaborative study promoted by “REEM: Red Española de Esclerosis Múltiple” (RETICS-REEM RD12/0032/009; www.reem.es). The funders did not play any role in: study design, data collection and analysis, decision to publish, or preparation of the manuscript.