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

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journal.pone.0090182.pdf (432.8Kb)
Date
2014-03-03
Author
De la Hera, Belén
Varadé, Jezabel
García-Montojo, Marta
Alcina, Antonio
Fedetz, María
Alloza Moral, Iraide
Astobiza Pérez, Janire
Leyva, Laura
Fernández, Óscar
Izquierdo, Guillermo
Antigüedad, Alfredo
Arroyo, Rafael
Álvarez-Lafuente, Roberto
Vandenbroeck, Koen
Matesanz, Fuencisla
Urcelay, Elena
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PLOS ONE 9(3) : (2014) // Article ID e90182
URI
http://hdl.handle.net/10810/17363
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; ORM-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, ORM-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.
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