[HTML][HTML] Functional variant in the autophagy-related 5 gene promotor is associated with childhood asthma
LJ Martin, J Gupta, SSSK Jyothula, M Butsch Kovacic… - PloS one, 2012 - journals.plos.org
LJ Martin, J Gupta, SSSK Jyothula, M Butsch Kovacic, JM Biagini Myers, TL Patterson…
PloS one, 2012•journals.plos.orgRationale and Objective 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. Methods Using genetic and experimental approaches,
we examined the association of 13 HapMap-derived tagging SNPs in ATG5 and ATG7 with …
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. Methods Using genetic and experimental approaches,
we examined the association of 13 HapMap-derived tagging SNPs in ATG5 and ATG7 with …
Rationale and Objective
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.
Methods
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.
Measurements and Main Results
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.
Conclusion
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.
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