Publication: Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations.
dc.contributor.author | Alcina, Antonio | |
dc.contributor.author | Fedetz, María | |
dc.contributor.author | Izquierdo, Guillermo | |
dc.contributor.author | Lucas, Miguel | |
dc.contributor.author | Fernández, Oscar | |
dc.contributor.author | Ndagire, Dorothy | |
dc.contributor.author | Catalá-Rabasa, Antonio | |
dc.contributor.author | Ruiz, Agustín | |
dc.contributor.author | Gayán, Javier | |
dc.contributor.author | Delgado, Concepción | |
dc.contributor.author | Arnal, Carmen | |
dc.contributor.author | Matesanz, Fuencisla | |
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.contributor.funder | This 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. | |
dc.date.accessioned | 2013-03-13T12:32:17Z | |
dc.date.available | 2013-03-13T12:32:17Z | |
dc.date.issued | 2012-01-13 | |
dc.description.abstract | The 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.version | Yes | es |
dc.identifier.citation | Alcina 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):e29819 | es |
dc.identifier.doi | 10.1371/journal.pone.0029819 | |
dc.identifier.essn | 1932-6203 | |
dc.identifier.pmc | PMC3258250 | |
dc.identifier.pmid | 22253788 | |
dc.identifier.uri | http://hdl.handle.net/10668/828 | |
dc.journal.title | PloS one | |
dc.language.iso | en | |
dc.publisher | Public Library of Science | es |
dc.publisher | Francesc Palau, Instituto de Ciencia de Materiales de Madrid - Instituto de Biomedicina de Valencia, Spain | es |
dc.relation.publisherversion | http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0029819 | es |
dc.rights.accessRights | open access | |
dc.subject | Adulto | es |
dc.subject | Alelos | es |
dc.subject | Grupo de Ascendencia Continental Europea | es |
dc.subject | Femenino | es |
dc.subject | Regulación de la Expresión Génica | es |
dc.subject | Estudios de Asociación Genética | es |
dc.subject | Predisposición Genética a la Enfermedad | es |
dc.subject | Genética de Población | es |
dc.subject | Estudio de Asociación del Genoma Completo | es |
dc.subject | Cadenas beta de HLA-DQ | es |
dc.subject | Cadenas HLA-DRB1 | es |
dc.subject | Cadenas HLA-DRB5 | es |
dc.subject | Haplotipos | es |
dc.subject | Humanos | es |
dc.subject | Desequilibrio de Ligamiento | es |
dc.subject | Modelos Logísticos | es |
dc.subject | Masculino | es |
dc.subject | Esclerosis Múltiple | es |
dc.subject | Polimorfismo de Nucleótido Simple | es |
dc.subject | Sitios de Carácter Cuantitativo | es |
dc.subject.mesh | Medical Subject Headings::Named Groups::Persons::Age Groups::Adult | es |
dc.subject.mesh | Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles | es |
dc.subject.mesh | Medical Subject Headings::Named Groups::Persons::Population Groups::Continental Population Groups::European Continental Ancestry Group | es |
dc.subject.mesh | Medical Subject Headings::Check Tags::Female | es |
dc.subject.mesh | Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation | es |
dc.subject.mesh | Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies | es |
dc.subject.mesh | Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease | es |
dc.subject.mesh | Medical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genetics, Population | es |
dc.subject.mesh | Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Molecular Epidemiology::Genome-Wide Association Study | es |
dc.subject.mesh | Medical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens::HLA-D Antigens::HLA-DQ Antigens::HLA-DQ beta-Chains | es |
dc.subject.mesh | Medical 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-Chains | es |
dc.subject.mesh | Medical 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 Chains | es |
dc.subject.mesh | Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Haplotypes | es |
dc.subject.mesh | Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans | es |
dc.subject.mesh | Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Linkage::Linkage Disequilibrium | es |
dc.subject.mesh | Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic Models | es |
dc.subject.mesh | Medical Subject Headings::Check Tags::Male | es |
dc.subject.mesh | Medical Subject Headings::Diseases::Immune System Diseases::Autoimmune Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis | es |
dc.subject.mesh | Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide | es |
dc.subject.mesh | Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genetic Loci::Quantitative Trait Loci | es |
dc.subject.mesh | Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors | es |
dc.title | Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations. | es |
dc.type | research article | |
dc.type.hasVersion | VoR | |
dspace.entity.type | Publication |
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