Functional variant in the autophagy-related 5 gene promotor is associated with childhood asthma.
<h4>Rationale and objective</h4>Autophagy 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 bet...
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2012
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oai:doaj.org-article:387c3faf46704aaca8344c0be9ea39da2021-11-18T07:21:29ZFunctional variant in the autophagy-related 5 gene promotor is associated with childhood asthma.1932-620310.1371/journal.pone.0033454https://doaj.org/article/387c3faf46704aaca8344c0be9ea39da2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22536318/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Rationale and objective</h4>Autophagy 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.<h4>Methods</h4>Using 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.<h4>Measurements and main results</h4>We 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 (p<0.05). We found that rs510432 was functionally relevant and conferred significantly increased promotor activity. Furthermore, Atg5 expression was increased in nasal epithelium of acute asthmatics compared to stable asthmatics and non-asthmatic controls.<h4>Conclusion</h4>Genetic 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.Lisa J MartinJayanta GuptaSoma S S K JyothulaMelinda Butsch KovacicJocelyn M Biagini MyersTia L PattersonMark B EricksenHua HeAaron M GibsonTesfaye M BayeSushil AmirisettyAnna M TsorasYoubao ShaN Tony EissaGurjit K Khurana HersheyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e33454 (2012) |
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Medicine R Science Q Lisa J Martin Jayanta Gupta Soma S S K Jyothula Melinda Butsch Kovacic Jocelyn M Biagini Myers Tia L Patterson Mark B Ericksen Hua He Aaron M Gibson Tesfaye M Baye Sushil Amirisetty Anna M Tsoras Youbao Sha N Tony Eissa Gurjit K Khurana Hershey Functional variant in the autophagy-related 5 gene promotor is associated with childhood asthma. |
| description |
<h4>Rationale and objective</h4>Autophagy 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.<h4>Methods</h4>Using 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.<h4>Measurements and main results</h4>We 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 (p<0.05). We found that rs510432 was functionally relevant and conferred significantly increased promotor activity. Furthermore, Atg5 expression was increased in nasal epithelium of acute asthmatics compared to stable asthmatics and non-asthmatic controls.<h4>Conclusion</h4>Genetic 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. |
| format |
article |
| author |
Lisa J Martin Jayanta Gupta Soma S S K Jyothula Melinda Butsch Kovacic Jocelyn M Biagini Myers Tia L Patterson Mark B Ericksen Hua He Aaron M Gibson Tesfaye M Baye Sushil Amirisetty Anna M Tsoras Youbao Sha N Tony Eissa Gurjit K Khurana Hershey |
| author_facet |
Lisa J Martin Jayanta Gupta Soma S S K Jyothula Melinda Butsch Kovacic Jocelyn M Biagini Myers Tia L Patterson Mark B Ericksen Hua He Aaron M Gibson Tesfaye M Baye Sushil Amirisetty Anna M Tsoras Youbao Sha N Tony Eissa Gurjit K Khurana Hershey |
| author_sort |
Lisa J Martin |
| title |
Functional variant in the autophagy-related 5 gene promotor is associated with childhood asthma. |
| title_short |
Functional variant in the autophagy-related 5 gene promotor is associated with childhood asthma. |
| title_full |
Functional variant in the autophagy-related 5 gene promotor is associated with childhood asthma. |
| title_fullStr |
Functional variant in the autophagy-related 5 gene promotor is associated with childhood asthma. |
| title_full_unstemmed |
Functional variant in the autophagy-related 5 gene promotor is associated with childhood asthma. |
| title_sort |
functional variant in the autophagy-related 5 gene promotor is associated with childhood asthma. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/387c3faf46704aaca8344c0be9ea39da |
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