自噬相关基因5启动子功能性变异与儿童期哮喘相关
2012/07/05
摘要
原理和目的：自噬是一个细胞生理过程，旨在清除或再循环细胞蛋白。近期研究显示，自噬参与了免疫功能异常、炎症性疾病的致病和病毒感染的反应。本试验研究自信信号通路中两个基因ATG5和ATG7在儿童期哮喘中的相互作用。
方法：采用遗传学实验方法，在312名哮喘儿童和246名非过敏性、哮喘控制儿童中，研究ATG5和ATG7的13个HapMap标记单核苷酸多态性（SNP）与儿童期哮喘的关系。采用独立队列和归集分析对结果进行分析。最后，评价哮喘与SNP的相关性。
检测指标和主要结果：结果显示，ATG5单核苷酸多态性rs12201458和rs510432与哮喘相关（P分别为0.00085和0.0025)。在3个独立队列中，相同连锁不平衡结构域中ATG5的额外变异与哮喘相关（P<0.05）。功能上，rs510432与哮喘相关，而且能增加启动子活性。此外，与稳定性哮喘患者和非哮喘患者相比，急性哮喘患者的鼻上皮细胞Atg5表达增加。
结论：ATG5的遗传变异（包括功能性启动子变异）与儿童期哮喘相关。研究结果为ATG5在儿童期哮喘中的作用提供了新的证据。
（林江涛 审校）
PLoS One. 2012;7(4):e33454. Epub 2012 Apr 20.
Functional Variant in the Autophagy-Related 5 Gene Promotor is Associated with Childhood Asthma.
Martin LJ, Gupta J, Jyothula SS, Butsch Kovacic M, Biagini Myers JM, Patterson TL, Ericksen MB, He H, Gibson AM, Baye TM, Amirisetty S, Tsoras AM, Sha Y, Eissa NT, Hershey GK.
Source
Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America.
Abstract
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.
PLoS One. 2012;7(4):e33454. Epub 2012 Apr 20.
原理和目的：自噬是一个细胞生理过程，旨在清除或再循环细胞蛋白。近期研究显示，自噬参与了免疫功能异常、炎症性疾病的致病和病毒感染的反应。本试验研究自信信号通路中两个基因ATG5和ATG7在儿童期哮喘中的相互作用。
方法：采用遗传学实验方法，在312名哮喘儿童和246名非过敏性、哮喘控制儿童中，研究ATG5和ATG7的13个HapMap标记单核苷酸多态性（SNP）与儿童期哮喘的关系。采用独立队列和归集分析对结果进行分析。最后，评价哮喘与SNP的相关性。
检测指标和主要结果：结果显示，ATG5单核苷酸多态性rs12201458和rs510432与哮喘相关（P分别为0.00085和0.0025)。在3个独立队列中，相同连锁不平衡结构域中ATG5的额外变异与哮喘相关（P<0.05）。功能上，rs510432与哮喘相关，而且能增加启动子活性。此外，与稳定性哮喘患者和非哮喘患者相比，急性哮喘患者的鼻上皮细胞Atg5表达增加。
结论：ATG5的遗传变异（包括功能性启动子变异）与儿童期哮喘相关。研究结果为ATG5在儿童期哮喘中的作用提供了新的证据。
（林江涛 审校）
PLoS One. 2012;7(4):e33454. Epub 2012 Apr 20.
Functional Variant in the Autophagy-Related 5 Gene Promotor is Associated with Childhood Asthma.
Martin LJ, Gupta J, Jyothula SS, Butsch Kovacic M, Biagini Myers JM, Patterson TL, Ericksen MB, He H, Gibson AM, Baye TM, Amirisetty S, Tsoras AM, Sha Y, Eissa NT, Hershey GK.
Source
Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America.
Abstract
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.
PLoS One. 2012;7(4):e33454. Epub 2012 Apr 20.
