Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease

• DOI: 10.1164/rccm.202106-1404oc
• Publication Date: 2021-11-11T22:41:01Z
• Authors: Auyon J. Ghosh; Brian D. Hobbs; Matthew Moll; Aabida Saferali; Adel Boueiz; Jeong H. Yun; Frank Sciurba; Lucas Barwick; Andrew H. Limper; Kevin Flaherty; Gerard Criner; Kevin K. Brown; Robert Wise; Fernando J. Martinez; David Lomas; Peter J. Castaldi; Vincent J. Carey; Dawn L. DeMeo; Michael H. Cho; Edwin K. Silverman; Craig P. Hersh; James D. Crapo; Edwin K. Silverman; Barry J. Make; Elizabeth A. Regan; Terri H. Beaty; Peter J. Castaldi; Michael H. Cho; Dawn L. DeMeo; Adel El-Boueiz; Marilyn G. Foreman; Auyon J. Ghosh; Lystra P. Hayden; Craig P. Hersh; Jacqueline Hetmanski; Brian D. Hobbs; John E. Hokanson; Wonji Kim; Nan Laird; Christoph Lange; Sharon M. Lutz; Merry-Lynn McDonald; Dmitry Prokopenko; Matthew Moll; Jarrett Morrow; Dandi Qiao; Aabida Saferali; Phuwanat Sakornsa...; Emily S. Wan; Jeong H. Yun; Juan Pablo Centeno; Jean-Paul Charbon...; Harvey O. Coxson; Craig J. Galban; MeiLan K. Han; Eric A. Hoffman; Stephen Humphries; Francine L. Jacobson; Philip F. Judy; Ella A. Kazerooni; Alex Kluiber; David A. Lynch; Pietro Nardelli; John D. Newell; Aleena Notary; Andrea Oh; James C. Ross; Raul San Jose Est...; Joyce Schroeder; Jered Sieren; Berend C. Stoel; Juerg Tschirren; Edwin Van Beek; Bram van Ginneken; Eva van Rikxoort; Gonzalo Vegas San...; Lucas Veitel; George R. Washko; Carla G. Wilson; Robert Jensen; Douglas Everett; Jim Crooks; Katherine Pratte; Matt Strand; Erin Austin; Gregory Kinney; Kendra A. Young; Surya P. Bhatt; Jessica Bon; Alejandro A. Diaz; Barry Make; Susan Murray; Elizabeth Regan; Xavier Soler; Russell P. Bowler; Katerina Kechris; Farnoush Banaei-K...; Jeffrey L. Curtis; Perry G. Pernicano; Nicola Hanania; Mustafa Atik; Aladin Boriek; Kalpatha Guntupalli; Elizabeth Guy; Amit Parulekar; Craig Hersh; George Washko; R. Graham Barr; John Austin; Belinda D’Souza; Byron Thomashow; Neil MacIntyre; H. Page McAdams; Lacey Washington; Charlene McEvoy; Joseph Tashjian; Robert Wise; Robert Brown; Nadia N. Hansel; Karen Horton; Allison Lambert; Nirupama Putcha; Richard Casaburi; Alessandra Adami; Matthew Budoff; Hans Fischer; Janos Porszasz; Harry Rossiter; William Stringer; Amir Sharafkhaneh; Charlie Lan; Christine Wendt; Brian Bell; Ken M. Kunisaki; Eric L. Flenaugh; Hirut Gebrekristos; Mario Ponce; Silanath Terpenning; Gloria Westney; Richard Rosiello; David Pace; Gerard Criner; David Ciccolella; Francis Cordova; Chandra Dass; Gilbert D’Alonzo; Parag Desai; Michael Jacobs; Steven Kelsen; Victor Kim; A. James Mamary; Nathaniel Marchetti; Aditi Satti; Kartik Shenoy; Robert M. Steiner; Alex Swift; Irene Swift; Maria Elena Vega-...; Mark Dransfield; William Bailey; Anand Iyer; Hrudaya Nath; J. Michael Wells; Douglas Conrad; Andrew Yen; Alejandro P. Come...; Karin F. Hoth; John Newell; Brad Thompson; Ella Kazerooni; Wassim Labaki; Craig Galban; Dharshan Vummidi; Joanne Billings; Abbie Begnaud; Tadashi Allen; Frank Sciurba; Divay Chandra; Joel Weissfeld; Antonio Anzueto; Sandra Adams; Diego Maselli-Cac...; Mario E. Ruiz; Harjinder Singh
• Keywords: Adult; Genetic Markers; Male; Chronic Obstructive; Heterozygote; Genotype; Chronic Obstructive Pulmonary Disease; Clinical Sciences; Respiratory System; Medical and Health Sciences; chronic obstructive pulmonary disease; Pulmonary Disease; Pulmonary Disease, Chronic Obstructive; 03 medical and health sciences; 0302 clinical medicine; Clinical Research; Cardiovascular Medicine and Haematology; 80 and over; 2.1 Biological and endogenous factors; Humans; Longitudinal Studies; Aetiology; Lung; Aged; Emphysema; Aged, 80 and over; Biomedical and Clinical Sciences; COPDGene Investigators; Whole Genome Sequencing; RNA sequencing; Middle Aged; Survival Analysis; Respiratory Function Tests; 3. Good health; meta-analysis; Phenotype; Case-Control Studies; alpha 1-Antitrypsin; Respiratory; alpha-1 antitrypsin; Female

Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) COPD.