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Título : HERV-W polymorphism in chromosome X is associated with multiple sclerosis risk and with differential expression of MSRV.
Autor : García-Montojo, Marta
Hera, Belén de la
Varadé, Jezabel
Encarnación, Ana de la
Camacho, Iris
Domínguez-Mozo, María
Árias-Leal, Ana
García-Martínez, Angel
Casanova, Ignacio
Izquierdo, Guillermo
Lucas, Miguel
Fedetz, Maria
Alcina, Antonio
Arroyo, Rafael
Matesanz, Fuencisla
Urcelay, Elena
Alvarez-Lafuente, Roberto
Filiación: [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.
Palabras clave : Multiple sclerosis
Human endogenous retrovirus
Multiple sclerosis associated retrovirus
Chromosome x
Gender differences
Cromosomas humanos X
Predisposición genética a la enfermedad
Retrovirus endógenos
Esclerosis múltiple
MeSH: Medical Subject Headings::Anatomy::Cells::Cellular Structures::Chromosomes::Chromosomes, Mammalian::Chromosomes, Human::Chromosomes, Human, 6-12 and X::Chromosomes, Human, X
Medical Subject Headings::Organisms::Viruses::RNA Viruses::Retroviridae::Endogenous Retroviruses
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle Aged
Medical Subject Headings::Diseases::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Assessment
Medical Subject Headings::Named Groups::Persons::Age Groups::Adult
Fecha de publicación : 9-Jan-2014
Editorial : BioMed Central
Cita Bibliográfica: García-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; 11:2
Abstract: BACKGROUND 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.
Descripción : Journal Article; Research Support, Non-U.S. Gov't;
Versión del editor :
DOI: 10.1186/1742-4690-11-2
ISSN : 1742-4690 (Online)
Appears in Collections:01- Artículos - Hospital Virgen Macarena

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