Evidence of new risk genetic factor to systemic lupus erythematosus: the UBASH3A gene
| Autor: | María Francisca González-Escribano, Lina-Marcela Diaz-Gallo, Norberto Ortego-Centeno, Torsten Witte, Enrique de Ramón, Francisco J. García-Hernández, Hans-Joachim Anders, José Mario Sabio, Elena Sánchez, Miguel A. González-Gay, Javier Martín |
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| Přispěvatelé: | [Diaz-Gallo,LM, Sánchez,E, Martin,J] Cellular Biology and Immunology Department, Instituto de Parasitología y Biomedicina ‘‘López-Neyra’’, Consejo Superior de Investigaciones Científicas (IPBLN- Consejo Superior de Investigaciones Científicas), Granada, Spain. [Ortego-Centeno,N] Department of Internal Medicine, Hospital Clínico San Cecilio, Granada, Spain. [Sabio,JM] Department of Internal Medicine, Hospital Virgen de las Nieves, Granada, Spain. [García-Hernández,FJ] Department of Internal Medicine, Hospital Virgen del Rocío, Sevilla, Spain. [Ramón,E de] Department of Internal Medicine, Hospital Carlos Haya, Málaga, Spain. [González-Gay,MA] Department of Rheumatology, Instituto de Formación e Investigación Marqués de Valdecilla, Hospital Universitario Marqués de Valdecilla, Santander, Spain. [Witte,T] Department of Clinical Immunology and Rheumatology, Hannover Medical School, Hannover, Germany. [Anders,HJ] Medical department and policlinic IV, Klinikum der Universitat, München, Munich, Germany. [González-Escribano,MF] Department of Immunology, Hospital Virgen del Rocío, Sevilla, Spain., This work was partially supported by RETICS Program, RD08/0075 (RIER) from Instituto de Salud Carlos III, within the VI PN de I+D+i 2008-2011 (FEDER) and grant KFO 250, TP 03, WI 1031/6-1 LMDG was supported by the 'Ayudas Predoctorales de Formación en Investigación en Salud (PFIS - FI09/00544)' from the 'Instituto de Salud Carlos III'. |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Genetic Screens
Linkage disequilibrium Desequilibrio de Ligamiento Epidemiology LOCI lcsh:Medicine Genome-wide association study ComputingMilieux_LEGALASPECTSOFCOMPUTING Autoimmunity Pathogenesis VARIANTS medicine.disease_cause Biochemistry Linkage Disequilibrium DISEASE Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings] Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] Risk Factors Genotype Genetics of the Immune System Lupus Erythematosus Systemic lcsh:Science ComputingMilieux_MISCELLANEOUS Multidisciplinary Genomics Humanos Genetic Epidemiology Cohort Medicine Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings] Alelos Research Article EXPRESSION UBASH3A protein human Quantitative Trait Loci Immunology Predisposición Genética a la Enfermedad Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Microbiology Systemic Lupus Erythematosus Autoimmune Diseases Diseases::Pathological Conditions Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease [Medical Subject Headings] Genomic Medicine Rheumatology Genome Analysis Tools Phenomena and Processes::Genetic Phenomena::Genetic Linkage [Medical Subject Headings] Genetic variation Genetics medicine Humans Genetic Predisposition to Disease Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Carrier Proteins::Adaptor Proteins Signal Transducing [Medical Subject Headings] Genetic Testing Allele GENOME-WIDE ASSOCIATION Alleles Genetic Association Studies Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings] Adaptor Proteins Signal Transducing Proteínas Adaptadoras Transductoras de Señales Clinical Genetics Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism Genetic::Polymorphism Single Nucleotide [Medical Subject Headings] Population Biology Lupus Eritematoso Sistémico lcsh:R Proteins Computational Biology Human Genetics Sitios de Carácter Cuantitativo Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genetic Loci::Quantitative Trait Loci [Medical Subject Headings] Diseases::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Lupus Erythematosus Systemic [Medical Subject Headings] Data_GENERAL Genetics of Disease Genetic Polymorphism T-Cell Receptors Clinical Immunology lcsh:Q Polimorfismo de Nucleótido Simple Population Genetics |
| Zdroj: | PLoS ONE, Vol 8, Iss 4, p e60646 (2013) Digital.CSIC. Repositorio Institucional del CSIC instname PLoS ONE |
| Popis: | Creative Commons Attribution License. The ubiquitin associated and Src-homology 3 (SH3) domain containing A (UBASH3a) is a suppressor of T-cell receptor signaling, underscoring antigen presentation to T-cells as a critical shared mechanism of diseases pathogenesis. The aim of the present study was to determine whether the UBASH3a gene influence the susceptibility to systemic lupus erythematosus (SLE) in Caucasian populations. We evaluated five UBASH3a polymorphisms (rs2277798, rs2277800, rs9976767, rs13048049 and rs17114930), using TaqMan (R) allelic discrimination assays, in a discovery cohort that included 906 SLE patients and 1165 healthy controls from Spain. The SNPs that exhibit statistical significance difference were evaluated in a German replication cohort of 360 SLE patients and 379 healthy controls. The case-control analysis in the Spanish population showed a significant association between the rs9976767 and SLE (Pc = 9.9E-03 OR = 1.21 95% CI = 1.07-1.37) and a trend of association for the rs2277798 analysis (P = 0.09 OR = 0.9 95% CI = 0.79-1.02). The replication in a German cohort and the meta-analysis confirmed that the rs9976767 (Pc = 0.02; Pc = 2.4E-04, for German cohort and meta-analysis, respectively) and rs2277798 (Pc = 0.013; Pc = 4.7E-03, for German cohort and meta-analysis, respectively) UBASH3a variants are susceptibility factors for SLE. Finally, a conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs9976767 polymorphism. Our results suggest that UBASH3a gene plays a role in the susceptibility to SLE. Moreover, our study indicates that UBASH3a can be considered as a common genetic factor in autoimmune diseases. RETICS Program from Instituto de Salud Carlos III [RD08/0075 (RIER) VI PN de I+D+i 2008-2011 (FEDER)].Ayudas Predoctorales de Formacion en Investigacion en Salud from the "Instituto de Salud Carlos III" KFO 250, TP 03, WI 1031/6-1 LMDG PFIS - FI09/00544 |
| Databáze: | OpenAIRE |
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