학술논문
Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease.
Document Type
article
Author
Ghosh, Auyon J; Hobbs, Brian D; Moll, Matthew; Saferali, Aabida; Boueiz, Adel; Yun, Jeong H; Sciurba, Frank; Barwick, Lucas; Limper, Andrew H; Flaherty, Kevin; Criner, Gerard; Brown, Kevin K; Wise, Robert; Martinez, Fernando J; Lomas, David; Castaldi, Peter J; Carey, Vincent J; DeMeo, Dawn L; Cho, Michael H; Silverman, Edwin K; Hersh, Craig P; Crapo, James D; Make, Barry J; Regan, Elizabeth A; Beaty, Terri H; El-Boueiz, Adel; Foreman, Marilyn G; Hayden, Lystra P; Hetmanski, Jacqueline; Hokanson, John E; Kim, Wonji; Laird, Nan; Lange, Christoph; Lutz, Sharon M; McDonald, Merry-Lynn; Prokopenko, Dmitry; Morrow, Jarrett; Qiao, Dandi; Sakornsakolpat, Phuwanat; Wan, Emily S; Centeno, Juan Pablo; Charbonnier, Jean-Paul; Coxson, Harvey O; Galban, Craig J; Han, MeiLan K; Hoffman, Eric A; Humphries, Stephen; Jacobson, Francine L; Judy, Philip F; Kazerooni, Ella A; Kluiber, Alex; Lynch, David A; Nardelli, Pietro; Newell, John D; Notary, Aleena; Oh, Andrea; Ross, James C; Estepar, Raul San Jose; Schroeder, Joyce; Sieren, Jered; Stoel, Berend C; Tschirren, Juerg; Van Beek, Edwin; van Ginneken, Bram; van Rikxoort, Eva; Sanchez-Ferrero, Gonzalo Vegas; Veitel, Lucas; Washko, George R; Wilson, Carla G; Jensen, Robert; Everett, Douglas; Crooks, Jim; Pratte, Katherine; Strand, Matt; Austin, Erin; Kinney, Gregory; Young, Kendra A; Bhatt, Surya P; Bon, Jessica; Diaz, Alejandro A; Make, Barry; Murray, Susan; Regan, Elizabeth; Soler, Xavier; Bowler, Russell P; Kechris, Katerina; Banaei-Kashani, Farnoush; Curtis, Jeffrey L; Pernicano, Perry G; Hanania, Nicola
Source
American Journal of Respiratory and Critical Care Medicine. 205(3)
Subject
Language
Abstract
Rationale: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. Objectives: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. Methods: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. Measurements and Main Results: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV1% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV1 was 3.9% lower (95% confidence interval [CI], -6.55% to -1.26%) and emphysema (the percentage of lung attenuation areas