García-Montojo, MartaHera, Belén de laVaradé, JezabelEncarnación, Ana de laCamacho, IrisDomínguez-Mozo, MaríaÁrias-Leal, AnaGarcía-Martínez, AngelCasanova, IgnacioIzquierdo, GuillermoLucas, MiguelFedetz, MariaAlcina, AntonioArroyo, RafaelMatesanz, FuencislaUrcelay, ElenaAlvarez-Lafuente, Roberto2015-03-192015-03-192014-01-09García-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; 11:2http://hdl.handle.net/10668/1850Journal Article; Research Support, Non-U.S. Gov't;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.enMultiple sclerosisHuman endogenous retrovirusHERV-WMultiple sclerosis associated retrovirusChromosome xSexGender differencesAutoimmunityCromosomas humanos XPredisposición genética a la enfermedadRetrovirus endógenosEsclerosis múltipleMedical Subject Headings::Anatomy::Cells::Cellular Structures::Chromosomes::Chromosomes, Mammalian::Chromosomes, Human::Chromosomes, Human, 6-12 and X::Chromosomes, Human, XMedical Subject Headings::Organisms::Viruses::RNA Viruses::Retroviridae::Endogenous RetrovirusesMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to DiseaseMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Diseases::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple SclerosisMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, GeneticMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk AssessmentMedical Subject Headings::Named Groups::Persons::Age Groups::AdultHERV-W polymorphism in chromosome X is associated with multiple sclerosis risk and with differential expression of MSRV.research article24405691open access10.1186/1742-4690-11-21742-4690PMC3892049