Functional Variant in the Autophagy-Related 5 Gene Promotor is Associated with Childhood Asthma
| Autor: | Tesfaye M. Baye, Sushil Amirisetty, Tia L. Patterson, Jocelyn M. Biagini Myers, Melinda Butsch Kovacic, Mark B. Ericksen, Anna M. Tsoras, Jayanta Gupta, Gurjit K. Khurana Hershey, Youbao Sha, Aaron M. Gibson, Lisa J. Martin, N. Tony Eissa, S. Jyothula, Hua He |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Pulmonology Transcription Genetic Epidemiology Ubiquitin-Activating Enzymes Bioinformatics Pediatrics Autophagy-Related Protein 7 Linkage Disequilibrium Autophagy-Related Protein 5 Pathogenesis 0302 clinical medicine Gene Frequency Genes Reporter Luciferases Firefly Gene expression Pediatric Epidemiology Child Promoter Regions Genetic 0303 health sciences Multidisciplinary 3. Good health Child Preschool 030220 oncology & carcinogenesis Medicine Female Microtubule-Associated Proteins Research Article medicine.medical_specialty Adolescent Science ATG5 Pediatric Pulmonology Biology Polymorphism Single Nucleotide 03 medical and health sciences Molecular genetics Genetics medicine Humans Genetic Association Studies Luciferases Renilla 030304 developmental biology Autophagy HEK 293 cells Computational Biology Human Genetics Sequence Analysis DNA Asthma Human genetics Nasal Mucosa HEK293 Cells Haplotypes Case-Control Studies Immunology Genetic Polymorphism Clinical Immunology Population Genetics |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 4, p e33454 (2012) |
| ISSN: | 1932-6203 |
| Popis: | Rationale and objectiveAutophagy is a cellular process directed at eliminating or recycling cellular proteins. Recently, the autophagy pathway has been implicated in immune dysfunction, the pathogenesis of inflammatory disorders, and response to viral infection. Associations between two genes in the autophagy pathway, ATG5 and ATG7, with childhood asthma were investigated.MethodsUsing genetic and experimental approaches, we examined the association of 13 HapMap-derived tagging SNPs in ATG5 and ATG7 with childhood asthma in 312 asthmatic and 246 non-allergic control children. We confirmed our findings by using independent cohorts and imputation analysis. Finally, we evaluated the functional relevance of a disease associated SNP.Measurements and main resultsWe demonstrated that ATG5 single nucleotide polymorphisms rs12201458 and rs510432 were associated with asthma (p = 0.00085 and 0.0025, respectively). In three independent cohorts, additional variants in ATG5 in the same LD block were associated with asthma (pConclusionGenetic variants in ATG5, including a functional promotor variant, are associated with childhood asthma. These results provide novel evidence for a role for ATG5 in childhood asthma. |
| Databáze: | OpenAIRE |
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