Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/828
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dc.contributor.authorAlcina, Antonio-
dc.contributor.authorFedetz, María-
dc.contributor.authorIzquierdo, Guillermo-
dc.contributor.authorLucas, Miguel-
dc.contributor.authorFernández, Oscar-
dc.contributor.authorNdagire, Dorothy-
dc.contributor.authorCatalá-Rabasa, Antonio-
dc.contributor.authorRuiz, Agustín-
dc.contributor.authorGayán, Javier-
dc.contributor.authorDelgado, Concepción-
dc.contributor.authorArnal, Carmen-
dc.contributor.authorMatesanz, Fuencisla-
dc.date.accessioned2013-03-13T12:32:17Z-
dc.date.available2013-03-13T12:32:17Z-
dc.date.issued2012-01-13-
dc.identifier.citationAlcina A, Abad-Grau Mdel M, Fedetz M, Izquierdo G, Lucas M, Fernández O, et al. Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations. PLoS ONE; 7(1):e29819es
dc.identifier.issn1932-6203 (Online)-
dc.identifier.otherPMC3258250-
dc.identifier.urihttp://hdl.handle.net/10668/828-
dc.description.abstractThe human leukocyte antigen (HLA) DRB1*1501 has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL) for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS). We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone.es
dc.description.sponsorshipThis work was supported by the Ministerio de Ciencia e Innovación - Fondos Feder [PN-SAF2009-11491 to AA], Junta de Andalucía [P07-CVI-02551 to AA], and Fondo de Investigación Sanitaria [FIS PI081636, CP10/00526 to FM]. MF and DN are holders of a fellowship from Fundación Española de Esclerosis Múltple (FEDEM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.es
dc.language.isoenes
dc.publisherPublic Library of Sciencees
dc.publisherFrancesc Palau, Instituto de Ciencia de Materiales de Madrid - Instituto de Biomedicina de Valencia, Spaines
dc.relation.ispartofPloS onees
dc.subjectAdultoes
dc.subjectAleloses
dc.subjectGrupo de Ascendencia Continental Europeaes
dc.subjectFemeninoes
dc.subjectRegulación de la Expresión Génicaes
dc.subjectEstudios de Asociación Genéticaes
dc.subjectPredisposición Genética a la Enfermedades
dc.subjectGenética de Poblaciónes
dc.subjectEstudio de Asociación del Genoma Completoes
dc.subjectCadenas beta de HLA-DQes
dc.subjectCadenas HLA-DRB1es
dc.subjectCadenas HLA-DRB5es
dc.subjectHaplotiposes
dc.subjectHumanoses
dc.subjectDesequilibrio de Ligamientoes
dc.subjectModelos Logísticoses
dc.subjectMasculinoes
dc.subjectEsclerosis Múltiplees
dc.subjectPolimorfismo de Nucleótido Simplees
dc.subjectSitios de Carácter Cuantitativoes
dc.subject.meshMedical Subject Headings::Named Groups::Persons::Age Groups::Adultes
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleleses
dc.subject.meshMedical Subject Headings::Named Groups::Persons::Population Groups::Continental Population Groups::European Continental Ancestry Groupes
dc.subject.meshMedical Subject Headings::Check Tags::Femalees
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulationes
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studieses
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::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genetics, Populationes
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Molecular Epidemiology::Genome-Wide Association Studyes
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens::HLA-D Antigens::HLA-DQ Antigens::HLA-DQ beta-Chainses
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::Histocompatibility Antigens Class II::HLA-D Antigens::HLA-DQ Antigens::HLA-DQ beta-Chainses
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::Histocompatibility Antigens Class II::HLA-D Antigens::HLA-DR Antigens::HLA-DR beta-Chains::HLA-DRB5 Chainses
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Haplotypeses
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humanses
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Linkage::Linkage Disequilibriumes
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic Modelses
dc.subject.meshMedical Subject Headings::Check Tags::Malees
dc.subject.meshMedical Subject Headings::Diseases::Immune System Diseases::Autoimmune 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, Genetic::Polymorphism, Single Nucleotidees
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genetic Loci::Quantitative Trait Locies
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factorses
dc.titleMultiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations.es
dc.typeinfo:eu-repo/semantics/articlees
dc.description.versionYeses
dc.identifier.pmid22253788-
dc.rights.accessRightsAcceso abiertoes
dc.identifier.doi10.1371/journal.pone.0029819-
dc.type.versioninfo:eu-repo/semantics/publishedes
dc.relation.publisherversionhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0029819es
dc.contributor.authoraffiliation[Alcina, A; Fedetz, M; Ndagire, D; Catalá-Rabasa, A; Matesanz,F] Instituto de Parasitología y Biomedicina ‘López Neyra’, Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), Granada, Spain [Abad-Grau,M del M] Departamento de Lenguajes y Sistemas Informáticos, CITIC, Universidad de Granada, Granada, Spain.[Izquierdo,G; Matesanz,F] Unidad de Esclerosis Múltiple, Hospital Virgen Macarena, Sevilla, Spain.[Lucas,M] Servicio de Biología Molecular, Hospital Virgen Macarena, Sevilla, Spain. [Fernández,O] Servicio de Neurología, Instituto de Neurociencias Clínicas, Hospital Carlos Haya, Málaga, Spain. [Ruiz,A; Gayán,J] Departamento de Genómica Estructural, Neocodex, Sevilla, Spain.[Delgado,C] Centro Regional de Transfusión Sanguínea Granada-Almería, Granada, Spain.[Arnal,C] Servicio de Neurología, Hospital Virgen de las Nieves, Granada, Spain.es
dc.type.subtypeArtículoes
Appears in Collections:01- Artículos - Hospital Regional de Málaga
01- Artículos - Hospital Virgen de las Nieves
01- Artículos - Hospital Virgen Macarena

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