1. HLA and non-HLA genes in Behçet¿s disease: a multicentric study in the Spanish population
- Author
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Miguel A. González-Gay, P. Fanlo, Genaro Graña-Gil, María Francisca González-Escribano, Norberto Ortego-Centeno, Ana Celia Barnosi-Marín, Javier Martín, Juan Sánchez-Bursón, Gerard Espinosa, Marta Conde-Jaldón, Roser Solans, Antonio Núñez-Roldán, Teresa Camps, José Raúl García-Lozano, M.A. Montes-Cano, María Jesús Castillo-Palma, Lourdes Ortiz-Fernández, Santos Castañeda, [Montes Cano,A, Conde-Jaldón,M, García-Lozano,J, Ortiz-Fernández,L, Núñez-Roldán,A, González-Escribano,MF] Servicio de Inmunología, IBiS, Hospital Universitario Virgen del Rocío/CSIC/ Universidad de Sevilla, Spain. [Ortego-Centeno,N] Servicio de Medicina Interna, Hospital Clínico San Cecilio, Granada, Spain. [Castillo-Palma,MJ] Servicio de Medicina Interna, Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Espinosa,G] Servicio de Enfermedades Autoinmunes, Hospital Clinic, Barcelona, Spain. [Graña-Gil,G] Servicio de Reumatología, CHU A Coruña, Spain. [González-Gay,MA] Servicio de Reumatología, Hospital Marques de Valdecilla, Santander, Spain. [Barnosi-Marín,AC] Servicio de Medicina Interna, Hospital Torrecárdenas, Almería, Spain. [Solans,R] Servicio de Medicina Interna, Hospital Vall d’Hebron, Barcelona, Spain. [Fanlo,P] Servicio de Medicina Interna, Hospital Virgen del Camino, Pamplona, Spain. [Camps,T] Servicio de Medicina Interna, Hospital Carlos Haya, Málaga, Spain. [Castañeda,S] Servicio de Reumatología, Hospital de la Princesa, Madrid, Spain. [Sánchez-Bursón,J] Servicio de Reumatología, Hospital de Valme, Sevilla, Spain. [Martín,J] IPB López Neyra, Granada, Spain., Fondo de Investigaciones Sanitarias (10/1701), Fondos FEDER, Plan Andaluz de Investigación (CTS-0197 and CTS-180), Red Enfermedades Inflamatorias y Reumáticas RD08/0075/0013 and Consejería de Salud de la Junta de Andalucía (PI0411/2010). LOF is the recipient of a fellowship (FI11/00547). The authors thank Asociación Andaluza de Enfermedades Autoinmunes (AADEA) and all patients and donors enrolled in the present study for their cooperation. Also, the authors thank the following public Spanish institutions for their participation in this study: Servicio Andaluz de Salud (Hospitales Torrecárdenas, Almería, Clínico San Cecilio, Granada, and Carlos Haya, Málaga, and Virgen del Rocío and Valme, Sevilla), Servei Catalá de la Salut (Clinic and Vall d’Hebron hospitals, Barcelona), Servizo Galego de Saude (Complejo Hospitalario Universitario, A Coruña), Servicio Cántabro de Salud (Hospital Marqués de Valdecilla, Santander), Servicio Navarro de Salud (Hospital Virgen del Camino, Pamplona), Servicio Montes-Cano et al. Arthritis Research & Therapy 2013, 15:R145
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Male ,Antígeno HLA-B35 ,Candidate gene ,Genome-wide association study ,Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Histocompatibility Antigens Class I::HLA-A Antigens [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings] ,Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens::HLA-B Antigens::HLA-B35 Antigen [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Receptores de Interleucina ,Gene Frequency ,Risk Factors ,HLA Antigens ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Statistical::Logistic Models [Medical Subject Headings] ,Immunology and Allergy ,Diseases::Stomatognathic Diseases::Mouth Diseases::Behcet Syndrome [Medical Subject Headings] ,Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings] ,Genetics ,education.field_of_study ,Behcet Syndrome ,Antígenos HLA-B ,Antígenos HLA-A ,Middle Aged ,Interleukin-10 ,Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens::HLA-B Antigens [Medical Subject Headings] ,Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens::HLA-B Antigens::HLA-B51 Antigen [Medical Subject Headings] ,HLA-B51 Antigen ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Interleukin [Medical Subject Headings] ,Female ,Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens [Medical Subject Headings] ,Interleucina-10 ,Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings] ,Antígeno HLA-B51 ,Research Article ,HLA-B57 antigen ,Adult ,Antígeno HLA-B57 ,Genotype ,Immunology ,Population ,Check Tags::Male [Medical Subject Headings] ,Single-nucleotide polymorphism ,Human leukocyte antigen ,Biology ,Polymorphism, Single Nucleotide ,Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings] ,Rheumatology ,IL23R protein, human ,Named Groups::Persons::Age Groups::Adult [Medical Subject Headings] ,HLA-B Antigens ,Humans ,Genetic Predisposition to Disease ,education ,Allele frequency ,Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings] ,HLA-A Antigens ,Antígeno HLA ,Receptors, Interleukin ,Minor allele frequency ,Logistic Models ,Check Tags::Female [Medical Subject Headings] ,Spain ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-10 [Medical Subject Headings] ,HLA-B35 Antigen ,Phenomena and Processes::Genetic Phenomena::Gene Frequency [Medical Subject Headings] ,Genome-Wide Association Study - Abstract
Introduction According to genome wide association (GWA) studies as well as candidate gene approaches, Behçet’s disease (BD) is associated with human leukocyte antigen (HLA)-A and HLA-B gene regions. The HLA-B51 has been consistently associated with the disease, but the role of other HLA class I molecules remains controversial. Recently, variants in non-HLA genes have also been associated with BD. The aims of this study were to further investigate the influence of the HLA region in BD and to explore the relationship with non-HLA genes recently described to be associated in other populations. Methods This study included 304 BD patients and 313 ethnically matched controls. HLA-A and HLA-B low resolution typing was carried out by PCR-SSOP Luminex. Eleven tag single nucleotide polymorphisms (SNPs) located outside of the HLA-region, previously described associated with the disease in GWA studies and having a minor allele frequency in Caucasians greater than 0.15 were genotyped using TaqMan assays. Phenotypic and genotypic frequencies were estimated by direct counting and distributions were compared using the χ2 test. Results In addition to HLA-B*51, HLA-B*57 was found as a risk factor in BD, whereas, B*35 was found to be protective. Other HLA-A and B specificities were suggestive of association with the disease as risk (A*02 and A*24) or protective factors (A*03 and B*58). Regarding the non-HLA genes, the three SNPs located in IL23R and one of the SNPs in IL10 were found to be significantly associated with susceptibility to BD in our population. Conclusion Different HLA specificities are associated with Behçet’s disease in addition to B*51. Other non-HLA genes, such as IL23R and IL-10, play a role in the susceptibility to the disease., This work was supported by Fondo de Investigaciones Sanitarias (10/1701), Fondos FEDER, Plan Andaluz de Investigación (CTS-0197 and CTS-180), Red Enfermedades Inflamatorias y Reumáticas RD08/0075/0013 and Consejería de Salud de la Junta de Andalucía (PI0411/2010). LOF is the recipient of a fellowship (FI11/00547).
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- 2013
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