Journal article
Alpha-1 Antitrypsin PiMZ Genotype Is Associated with Chronic Obstructive Pulmonary Disease in Two Racial Groups
Annals of the American Thoracic Society, Vol.14(8), pp.1280-1287
08/2017
DOI: 10.1513/AnnalsATS.201611-838OC
PMCID: PMC5566271
PMID: 28380308
Abstract
Rationale:
Alpha-1 antitrypsin deficiency, caused primarily by homozygosity for the Z allele of the
SERPINA1
gene, is a well-established genetic cause of chronic obstructive pulmonary disease (COPD). Whether the heterozygous PiMZ genotype for alpha-1 antitrypsin confers increased risk for COPD has been debated.
Objectives:
We analyzed 8,271 subjects in the Genetic Epidemiology of COPD (COPDGene) Study, hypothesizing that PiMZ would independently associate with COPD and COPD-related phenotypes.
Methods:
The COPDGene Study comprises a multiethnic, cross-sectional, observational cohort of non-Hispanic white and African American current and former smokers with at least 10 pack-years of smoking who were enrolled for detailed clinical and genetic studies of COPD and COPD-related traits. We performed multivariate logistic regression analysis for moderate to severe COPD and assessed Pi genotype with other relevant covariates in models stratified by race. We analyzed quantitative characteristics on the basis of volumetric computed tomography with generalized linear models controlling for genotype, scanner type, and similar covariates.
Results:
White PiMZ COPDGene subjects had significantly lower lung function, FEV
1
percent predicted (68 ± 28 vs. 75 ± 27;
P
= 0.0005), and FEV
1
/FVC ratio (0.59 ± 0.18 vs. 0.63 ± 0.17;
P
= 0.0008), as well as more radiographic emphysema (
P
= 0.001), than subjects without alpha-1 antitrypsin Z risk alleles. Similarly, African American PiMZ subjects had lower lung function, FEV
1
percent predicted (65 ± 33 vs. 84 ± 25;
P
= 0.009) and FEV
1
/FVC (0.61 ± 0.21 vs. 0.71 ± 0.15;
P
= 0.03).
Conclusions:
In the COPDGene Study, we demonstrate that PiMZ heterozygous individuals who smoke are at increased risk for COPD and obstructive lung function impairment compared with Z-allele noncarriers, regardless of race. Although severe alpha-1 antitrypsin deficiency is uncommon in African Americans, our study adds further support for initial targeted detection of all subjects with COPD for alpha-1 antitrypsin deficiency, including African Americans.
Clinical trial registered with
www.clinicaltrials.gov
(NCT00608784).
Details
- Title: Subtitle
- Alpha-1 Antitrypsin PiMZ Genotype Is Associated with Chronic Obstructive Pulmonary Disease in Two Racial Groups
- Creators
- Marilyn G Foreman - Morehouse School of Medicine, Atlanta, GeorgiaCarla Wilson - National Jewish Health, Denver, ColoradoDawn L DeMeo - Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MassachusettsCraig P Hersh - Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MassachusettsTerri H Beaty - Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MarylandMichael H Cho - Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MassachusettsJohn Ziniti - Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MassachusettsDouglas Curran-Everett - National Jewish Health, Denver, ColoradoGerard Criner - School of Medicine, Temple University, Philadelphia, Pennsylvania; andJohn E Hokanson - School of Public Health, University of Colorado, Denver, ColoradoMark Brantly - College of Medicine, University of Florida, Gainesville, FloridaFarshid N Rouhani - College of Medicine, University of Florida, Gainesville, FloridaRobert A Sandhaus - National Jewish Health, Denver, ColoradoJames D Crapo - National Jewish Health, Denver, ColoradoGenetic Epidemiology of COPD (COPDGene) Investigators
- Contributors
- Eric A Hoffman (Contributor) - University of Iowa, Radiology
- Resource Type
- Journal article
- Publication Details
- Annals of the American Thoracic Society, Vol.14(8), pp.1280-1287
- DOI
- 10.1513/AnnalsATS.201611-838OC
- PMID
- 28380308
- PMCID
- PMC5566271
- NLM abbreviation
- Ann Am Thorac Soc
- ISSN
- 2329-6933
- eISSN
- 2325-6621
- Publisher
- American Thoracic Society
- Language
- English
- Date published
- 08/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984051583802771
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