ArticlePloS one2012
SERPINA1 PiZ and PiS heterozygotes and lung function decline in the SAPALDIA cohort.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 48 citations in OpenAlex.
- α‑1 Antitrypsin is a potential target of inflammation and immunomodulation (Review).Molecular medicine reports · 2025Review
- Proteomic associations with forced expiratory volume: a Mendelian randomisation study.Respiratory research · 2024Article
- Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease.American journal of respiratory and critical care medicine · 2022Article
- Pleiotropic associations of heterozygosity for theERJ open research · 2021Article
- The Effects of RareAmerican journal of respiratory and critical care medicine · 2020Article
- Haplotype inInternational journal of molecular sciences · 2019Article
- Genome-wide association study of lung function and clinical implication in heavy smokers.BMC medical genetics · 2018Article
- Update on αBreathe (Sheffield, England) · 2018Review
- COPD in individuals with the PiMZ alpha-1 antitrypsin genotype.European respiratory review : an official journal of the European Respiratory Society · 2017Review
- Alpha-1 Antitrypsin PiMZ Genotype Is Associated with Chronic Obstructive Pulmonary Disease in Two Racial Groups.Annals of the American Thoracic Society · 2017Observational
- Whole exome sequencing identifies novel candidate genes that modify chronic obstructive pulmonary disease susceptibility.Human genomics · 2016Article
- Low serum levels of alpha1 anti-trypsin (α1-AT) and risk of airflow obstruction in non-primary α1-AT-deficient patients with compensated chronic liver disease.Medical science monitor : international medical journal of experimental and clinical research · 2015Observational
- Modification of the association between PM10 and lung function decline by cadherin 13 polymorphisms in the SAPALDIA cohort: a genome-wide interaction analysis.Environmental health perspectives · 2015Article
- Causal and synthetic associations of variants in the SERPINA gene cluster with alpha1-antitrypsin serum levels.PLoS genetics · 2013Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSevere alpha1-antitrypsin (AAT) deficiency is a strong risk factor for COPD. But the impact of gene variants resulting in mild or intermediate AAT deficiency on the longitudinal course of respiratory health remains controversial. There is indication from experimental studies that pro-inflammatory agents like cigarette smoke can interact with these variants and thus increase the risk of adverse respiratory health effects. Therefore, we tested the effect of the presence of a protease inhibitor (Pi) S or Z allele (PiMS and PiMZ) on the change in lung function in different inflammation-exposed subgroups of a large, population-based cohort study. METHODOLOGY AND PRINCIPAL
findingsThe SAPALDIA population includes over 4600 subjects from whom SERPINA1 genotypes for S and Z alleles, spirometry and respiratory symptoms at baseline and after 11 years follow-up, as well as proxies for inflammatory conditions, such as detailed smoking history, obesity and high sensitivity C-reactive protein (hs-CRP), were available. All analyses were performed by applying multivariate regression models. There was no overall unfavourable effect of PiMS or PiMZ genotype on lung function change. We found indication that PiZ heterozygosity interacted with inflammatory stimuli leading to an accelerated decline in measures in use as indices for assessing mild airway obstruction. Obese individuals with genotype PiMM had an average annual decline in the forced mid expiratory flow (ΔFEF25-75%) of 58.4 ml whereas in obese individuals with PiMZ it amounted to 92.2 ml (p = 0.03). Corresponding numbers for persistent smokers differed even more strongly (66.8 ml (PiMM) vs. 108.2 ml (PiMZ), p = 0.005). Equivalent, but less strong associations were observed for the change in the FEV1/FVC ratio.
conclusionsWe suggest that, in addition to the well established impact of the rare PiZZ genotype, one Z allele may be sufficient to accelerate lung function decline in population subgroups characterized by elevated levels of low grade inflammation.
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