Human endogenous retrovirus HERV-Fc1 association with multiple sclerosis susceptibility: a meta-analysis

• Published in: PloS one Vol. 9; no. 3; p. e90182
• Main Authors: de la Hera, Belén, Varadé, Jezabel, García-Montojo, Marta, Alcina, Antonio, Fedetz, María, Alloza, Iraide, Astobiza, Ianire, Leyva, Laura, Fernández, Oscar, Izquierdo, Guillermo, Antigüedad, Alfredo, Arroyo, Rafael, Álvarez-Lafuente, Roberto, Vandenbroeck, Koen, Matesanz, Fuencisla, Urcelay, Elena
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03-03-2014; Public Library of Science (PLoS)
• Subjects: Adult; Biology; Cohort Studies; Development and progression; Disease Susceptibility; Endogenous Retroviruses - isolation & purification; Female; Genetic aspects; Genomics; Health aspects; Humans; Infection; Male; Mathematics; Medicine; Meta-analysis; Middle Aged; Multiple sclerosis; Multiple Sclerosis - virology; Single nucleotide polymorphisms
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0090182

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.
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.
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: pM-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 [pM-H = 0.0003, ORM-H (95% CI) = 1.32 (1.14-1.53)].
Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.