Observational studyAnnals of the American Thoracic Society2017
Alpha-1 Antitrypsin PiMZ Genotype Is Associated with Chronic Obstructive Pulmonary Disease in Two Racial Groups.
Observational study in Annals of the American Thoracic Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00608784, which is not on this map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Diagnosis and treatment of lung disease associated with alpha one-antitrypsin deficiency: A position statement from the Thoracic Society of Australia and New Zealand.Respirology (Carlton, Vic.) · 2020Guideline
- Comment: Increased exacerbations and hospitalizations among Pi*MZ compared to Pi*MM individuals?Respiratory research · 2026Article
- Z variant heterozygosity in alpha-1 antitrypsin deficiency: disease risk and treatment implications.Orphanet journal of rare diseases · 2026Article
- Alpha-1 Antitrypsin Deficiency Beyond COPD and Emphysema: A Narrative Review.Medical sciences (Basel, Switzerland) · 2026Review
- Matrix metalloproteinases and disease severity among PI*MZ and PI*ZZ individuals in the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) cohort.BMJ open respiratory research · 2025Article
- Phenotypic Expression of Respiratory Diseases and Tailored Treatment in Patients with Intermediate Alpha-1 Antitrypsin Deficiency: Evidence from a Retrospective Analysis of a Selected Cohort of Patients.Medicina (Kaunas, Lithuania) · 2025Article
- αThe journal of allergy and clinical immunology. In practice · 2025Article
- Longitudinal Outcomes in Pi*MZ Alpha-1 Antitrypsin-Deficient Individuals with Tobacco Smoking History from the SPIROMICS Cohort.Annals of the American Thoracic Society · 2025Article
- Further Insights into Emphysema Progression and Lung Function Decline in MZ Alpha-1 Antitrypsin Deficiency.Annals of the American Thoracic Society · 2025Article
- Alpha-1 antitrypsin deficiency-associated liver disease: From understudied disorder to the poster child of genetic medicine.Hepatology communications · 2025Review
- Novel Lobe-based Transformer model (LobTe) to predict emphysema progression in Alpha-1 Antitrypsin Deficiency.Computers in biology and medicine · 2025Article
- Alpha-1 antitrypsin deficiency and Pi*Z allele as important co-factors in the development of liver fibrosis.World journal of hepatology · 2024Article
- Prevalence of Alpha-1 Antitrypsin Deficiency Alleles in a Lithuanian Cohort of Wheezing Small Children.Advances in respiratory medicine · 2024Article
- Prevalence of alpha-1 antitrypsin deficiency in patients with acute exacerbation of chronic obstructive pulmonary disease: Insights from a prospective study.Journal of family medicine and primary care · 2024Article
- Alpha-1 Antitrypsin Phenotyping: An Unmet Educational Need of Healthcare Providers.Journal of clinical medicine research · 2024Article
- Alpha-1 Antitrypsin PI M Heterozygotes with Rare Variants: Do They Need a Clinical and Functional Follow-Up?Journal of clinical medicine · 2024Article
- Prevalence of Chronic Obstructive Pulmonary Disease and Its Associated Risk Factors in Yunnan Province, China: A Population Based Cross-Sectional Study.International journal of chronic obstructive pulmonary disease · 2024Article
- Alpha-1 Antitrypsin Gene Variants in Patients without Severe Deficiency Diagnosed with Pulmonary Emphysema on Chest CT.International journal of chronic obstructive pulmonary disease · 2024Article
- Testing Alpha-1 Antitrypsin Deficiency in Black Populations.Advances in respiratory medicine · 2023Review
- Asthma and Chronic Obstructive Pulmonary Disease.Clinics in chest medicine · 2023Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 1 country.
Funding
Abstract
rationaleAlpha-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.
objectivesWe analyzed 8,271 subjects in the Genetic Epidemiology of COPD (COPDGene) Study, hypothesizing that PiMZ would independently associate with COPD and COPD-related phenotypes.
methodsThe 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.
resultsWhite PiMZ COPDGene subjects had significantly lower lung function, FEV
conclusionsIn 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).
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