aquaporin 5 polymorphisms and rate of lung function decline in chronic obstructive pulmonary disease水通道蛋白5多态性和慢性阻塞性肺疾病的肺功能下降.pdfVIP

Aquaporin 5 Polymorphisms and Rate of Lung Function Decline in Chronic Obstructive Pulmonary Disease 1,2 1 1 1 1 Nadia N. Hansel , Venkataramana Sidhaye , Nicholas M. Rafaels , Li Gao , Peisong Gao , Renaldo 1 3 2 1 1 1 Williams , John E. Connett , Terri H. Beaty , Rasika A. Mathias , Robert A. Wise , Landon S. King , Kathleen C. Barnes1* 1 Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America, 2 Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America, 3 Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America Abstract Rationale: Aquaporin-5 (AQP5) can cause mucus overproduction and lower lung function. Genetic variants in the AQP5 gene might be associated with rate of lung function decline in chronic obstructive pulmonary disease (COPD). Methods: Five single nucleotide polymorphisms (SNPs) in AQP5 were genotyped in 429 European American individuals with COPD randomly selected from the NHLBI Lung Health Study. Mean annual decline in FEV1 % predicted, assessed over five years, was calculated as a linear regression slope, adjusting for potential covariates and stratified by smoking status. Constructs containing the wildtype allele and risk allele of the coding SNP N228K were generated using site-directed mutagenesis, and transfected into HBE-16 (human bronchial epithelial cell line). AQP5 abundance and localization were assessed by immunoblots and confocal immunofluoresence und