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

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2014-03-03

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Hera, Belén de la
Varadé, Jezabel
García-Montojo, Marta
Alcina, Antonio
Fedetz, María
Alloza, Iraide
Astobiza, Ianire
Leyva, Laura
Fernández, Oscar
Izquierdo, Guillermo

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Public Library of Science
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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: 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.

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Journal Article; Research Support, Non-U.S. Gov't;

MeSH Terms

Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Diseases::Nervous System Diseases::Demyelinating Diseases::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis
Medical Subject Headings::Organisms::Viruses::RNA Viruses::Retroviridae::Endogenous Retroviruses
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Chromosomes::Sex Chromosomes::X Chromosome
Medical Subject Headings::Named Groups::Persons::Population Groups::Continental Population Groups::European Continental Ancestry Group
Medical Subject Headings::Geographicals::Geographic Locations::Europe::Spain
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic
Medical Subject Headings::Named Groups::Persons::Population Groups::Ethnic Groups
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies

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Keywords

Humanos, Esclerosis multiple, Retrovirus endógenos, Genoma, Cromosoma X, Grupo de ascendencia continental europea, España, Polimorfismo genético, Grupos étnicos, Estudios de cohortes

Citation

Hera 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):e90182