Hera, Belén de laVaradé, JezabelGarcía-Montojo, MartaAlcina, AntonioFedetz, MaríaAlloza, IraideAstobiza, IanireLeyva, LauraFernández, OscarIzquierdo, GuillermoAntigüedad, AlfredoArroyo, RafaelÁlvarez-Lafuente, RobertoVandenbroeck, KoenMatesanz, FuencislaUrcelay, Elena2014-06-092014-06-092014-03-03Hera B de la, Varadé J, García-Montojo M, Alcina A, Fedetz M, Alloza I, et al. Human endogenous retrovirus HERV-Fc1 association with multiple sclerosis susceptibility: a meta-analysis. PLoS ONE. 2014; 9(3):e90182http://hdl.handle.net/10668/1627Journal Article; Research Support, Non-U.S. Gov't;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)]. CONCLUSION Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.enHumanosEsclerosis multipleRetrovirus endógenosGenomaCromosoma XGrupo de ascendencia continental europeaEspañaPolimorfismo genéticoGrupos étnicosEstudios de cohortesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Nervous System Diseases::Demyelinating Diseases::Demyelinating Autoimmune Diseases, CNS::Multiple SclerosisMedical Subject Headings::Organisms::Viruses::RNA Viruses::Retroviridae::Endogenous RetrovirusesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::GenomeMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Chromosomes::Sex Chromosomes::X ChromosomeMedical Subject Headings::Named Groups::Persons::Population Groups::Continental Population Groups::European Continental Ancestry GroupMedical Subject Headings::Geographicals::Geographic Locations::Europe::SpainMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, GeneticMedical Subject Headings::Named Groups::Persons::Population Groups::Ethnic GroupsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studiesresearch article24594754open access10.1371/journal.pone.00901821932-6203PMC3971560