Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/828
Título : Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations.
Autor : Alcina, Antonio
Fedetz, María
Izquierdo, Guillermo
Lucas, Miguel
Fernández, Oscar
Ndagire, Dorothy
Catalá-Rabasa, Antonio
Ruiz, Agustín
Gayán, Javier
Delgado, Concepción
Arnal, Carmen
Matesanz, Fuencisla
Filiación: [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.
Palabras clave : Adulto
Alelos
Grupo de Ascendencia Continental Europea
Femenino
Regulación de la Expresión Génica
Estudios de Asociación Genética
Predisposición Genética a la Enfermedad
Genética de Población
Estudio de Asociación del Genoma Completo
Cadenas beta de HLA-DQ
Cadenas HLA-DRB1
Cadenas HLA-DRB5
Haplotipos
Humanos
Desequilibrio de Ligamiento
Modelos Logísticos
Masculino
Esclerosis Múltiple
Polimorfismo de Nucleótido Simple
Sitios de Carácter Cuantitativo
MeSH: Medical Subject Headings::Named Groups::Persons::Age Groups::Adult
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles
Medical Subject Headings::Named Groups::Persons::Population Groups::Continental Population Groups::European Continental Ancestry Group
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Association Studies
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease
Medical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genetics, Population
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Molecular Epidemiology::Genome-Wide Association Study
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
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
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
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Haplotypes
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Linkage::Linkage Disequilibrium
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic Models
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Diseases::Immune System Diseases::Autoimmune 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::Polymorphism, Single Nucleotide
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genetic Loci::Quantitative Trait Loci
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors
Fecha de publicación : 13-Jan-2012
Editorial : Public Library of Science
Francesc Palau, Instituto de Ciencia de Materiales de Madrid - Instituto de Biomedicina de Valencia, Spain
Cita Bibliográfica: 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
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.
URI: http://hdl.handle.net/10668/828
Versión del editor : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0029819
DOI: 10.1371/journal.pone.0029819
ISSN : 1932-6203 (Online)
Appears in Collections:01- Artículos - Hospital Virgen Macarena
01- Artículos - Hospital Virgen de las Nieves
01- Artículos - Hospital Regional de Málaga

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