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HERV-W polymorphism in chromosome X is associated with multiple sclerosis risk and with differential expression of MSRV.

dc.contributor.authorGarcía-Montojo, Marta
dc.contributor.authorHera, Belén de la
dc.contributor.authorVaradé, Jezabel
dc.contributor.authorEncarnación, Ana de la
dc.contributor.authorCamacho, Iris
dc.contributor.authorDomínguez-Mozo, María
dc.contributor.authorÁrias-Leal, Ana
dc.contributor.authorGarcía-Martínez, Angel
dc.contributor.authorCasanova, Ignacio
dc.contributor.authorIzquierdo, Guillermo
dc.contributor.authorLucas, Miguel
dc.contributor.authorFedetz, Maria
dc.contributor.authorAlcina, Antonio
dc.contributor.authorArroyo, Rafael
dc.contributor.authorMatesanz, Fuencisla
dc.contributor.authorUrcelay, Elena
dc.contributor.authorAlvarez-Lafuente, Roberto
dc.contributor.authoraffiliation[García-Montojo,M; Domínguez-Mozo,M; Árias-Leal,A; Casanova,I; Arroyo,R] Multiple Sclerosis Unit, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid. [Hera,B de la; Varadé,J; Encarnación,A de la; Camacho,I; García-Martínez,A; Urcelay,E; Alvarez-Lafuente,R] Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain. [Izquierdo,G] Multiple Sclerosis Unit, Hospital Virgen Macarena, Sevilla, Spain. [Lucas,M] Molecular Biology Department, Hospital Virgen Macarena, Sevilla, Spain. [Fedetz,M; Alcina,A; Matesanz,F] Instituto de Parasitologia y Biomedicina ’Lopez-Neyra’-CSIC, Parque Tecnológico de Ciencias de la Salud, Armilla (Granada), Spain.es
dc.contributor.funderInstituto de Salud Carlos III-Fondo Investigaciones Sanitarias FIS (10/01985 and 09/02074), Fundación Genzyme, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, and Fundación LAIR.
dc.date.accessioned2015-03-19T09:07:46Z
dc.date.available2015-03-19T09:07:46Z
dc.date.issued2014-01-09
dc.descriptionJournal Article; Research Support, Non-U.S. Gov't;es
dc.description.abstractBACKGROUND Multiple Sclerosis (MS) is an autoimmune demyelinating disease that occurs more frequently in women than in men. Multiple Sclerosis Associated Retrovirus (MSRV) is a member of HERV-W, a multicopy human endogenous retroviral family repeatedly implicated in MS pathogenesis. MSRV envelope protein is elevated in the serum of MS patients and induces inflammation and demyelination but, in spite of this pathogenic potential, its exact genomic origin and mechanism of generation are unknown. A possible link between the HERV-W copy on chromosome Xq22.3, that contains an almost complete open reading frame, and the gender differential prevalence in MS has been suggested. RESULTS MSRV transcription levels were higher in MS patients than in controls (U-Mann-Whitney; p = 0.004). Also, they were associated with the clinical forms (Spearman; p = 0.0003) and with the Multiple Sclerosis Severity Score (MSSS) (Spearman; p = 0.016). By mapping a 3 kb region in Xq22.3, including the HERV-W locus, we identified three polymorphisms: rs6622139 (T/C), rs6622140 (G/A) and rs1290413 (G/A). After genotyping 3127 individuals (1669 patients and 1458 controls) from two different Spanish cohorts, we found that in women rs6622139 T/C was associated with MS susceptibility: [χ2; p = 0.004; OR (95% CI) = 0.50 (0.31-0.81)] and severity, since CC women presented lower MSSS scores than CT (U-Mann-Whitney; p = 0.039) or TT patients (U-Mann-Whitney; p = 0.031). Concordantly with the susceptibility conferred in women, rs6622139*T was associated with higher MSRV expression (U-Mann-Whitney; p = 0.003). CONCLUSIONS Our present work supports the hypothesis of a direct involvement of HERV-W/MSRV in MS pathogenesis, identifying a genetic marker on chromosome X that could be one of the causes underlying the gender differences in MS.es
dc.description.versionYeses
dc.identifier.citationGarcía-Montojo M, de la Hera B, Varadé J, Encarnación A de la, Camacho I, Domínguez-Mozo M, et al. HERV-W polymorphism in chromosome X is associated with multiple sclerosis risk and with differential expression of MSRV. Retrovirology. 2014; 11:2es
dc.identifier.doi10.1186/1742-4690-11-2
dc.identifier.essn1742-4690
dc.identifier.pmcPMC3892049
dc.identifier.pmid24405691
dc.identifier.urihttp://hdl.handle.net/10668/1850
dc.journal.titleRetrovirology
dc.language.isoen
dc.publisherBioMed Centrales
dc.relation.publisherversionhttp://www.retrovirology.com/content/11/1/2/abstractes
dc.rights.accessRightsopen access
dc.subjectMultiple sclerosises
dc.subjectHuman endogenous retroviruses
dc.subjectHERV-Wes
dc.subjectMultiple sclerosis associated retroviruses
dc.subjectChromosome xes
dc.subjectSexes
dc.subjectGender differenceses
dc.subjectAutoimmunityes
dc.subjectCromosomas humanos Xes
dc.subjectPredisposición genética a la enfermedades
dc.subjectRetrovirus endógenoses
dc.subjectEsclerosis múltiplees
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Cellular Structures::Chromosomes::Chromosomes, Mammalian::Chromosomes, Human::Chromosomes, Human, 6-12 and X::Chromosomes, Human, Xes
dc.subject.meshMedical Subject Headings::Organisms::Viruses::RNA Viruses::Retroviridae::Endogenous Retroviruseses
dc.subject.meshMedical Subject Headings::Check Tags::Femalees
dc.subject.meshMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Diseasees
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humanses
dc.subject.meshMedical Subject Headings::Check Tags::Malees
dc.subject.meshMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Agedes
dc.subject.meshMedical Subject Headings::Diseases::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosises
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetices
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Assessmentes
dc.subject.meshMedical Subject Headings::Named Groups::Persons::Age Groups::Adultes
dc.titleHERV-W polymorphism in chromosome X is associated with multiple sclerosis risk and with differential expression of MSRV.es
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication

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