title: Human endogenous retrovirus HERV-Fc1 association with multiple sclerosis susceptibility: a meta-analysis.
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: 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)].
  
  
  CONCLUSIONS
  Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.
authors.affiliation: Immunology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: de la Hera
authors.affiliation: Immunology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Jezabel
authors.initials: J
authors.lastname: Varadé
authors.affiliation: Multiple Sclerosis Unit, Neurology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: García-Montojo
authors.affiliation: Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcina
authors.affiliation: Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Fedetz
authors.affiliation: Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Leioa, Spain.
authors.forename: Iraide
authors.initials: I
authors.lastname: Alloza
authors.affiliation: Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Leioa, Spain.
authors.forename: Ianire
authors.initials: I
authors.lastname: Astobiza
authors.affiliation: Laboratorio de Investigación, Instituto de Neurociencias Clínicas, Hospital Regional Universitario, Málaga, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Leyva
authors.affiliation: Servicio de Neurología, Instituto de Neurociencias Clínicas, Hospital Regional Universitario, Málaga, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernández
authors.affiliation: Unidad de Esclerosis Múltiple, Hospital Virgen Macarena, Sevilla, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.affiliation: Servicio de Neurología, Hospital de Basurto, Bilbao, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Antigüedad
authors.affiliation: Multiple Sclerosis Unit, Neurology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Arroyo
authors.affiliation: Multiple Sclerosis Unit, Neurology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Álvarez-Lafuente
authors.affiliation: Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Leioa, Spain; Achucarro Basque Center for Neuroscience - UPV/EHU, Zamudio, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
authors.forename: Koen
authors.initials: K
authors.lastname: Vandenbroeck
authors.affiliation: Instituto de Parasitología y Biomedicina "López Neyra", Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain.
authors.forename: Fuencisla
authors.initials: F
authors.lastname: Matesanz
authors.affiliation: Immunology Dept., Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004198:Disease Susceptibility; D020077:Endogenous Retroviruses / Q000302:isolation & purification*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000821:virology*