Pi\*S and Pi\*Z alpha 1 antitrypsin polymorphism and the risk for asbestosis in occupational exposure to asbestos

Our plain-English summary of Pi*S and Pi*Z alpha 1 antitrypsin polymorphism and the risk for asbestosis in occupational exposure to asbestos, by M.J. Lafuente, X. Casterad, N. Laso, et al (Toxicology Letters, 2002).

The study

• Authors: M.J. Lafuente, X. Casterad, N. Laso, S. Mas, R. Panades, A. Calleja, S. Hernandez, D. Turuguet, A. Ballesta, C. Ascaso, A. Lafuente
• Journal: Toxicology Letters
• Published: 2002;136(1):9-17
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Alpha 1 antitrypsin is a highly polymorphic anti-elastase enzyme, especially active in the protection of alveoli and liver. Here we studied the distribution of two deficient alleles Pi*Z and Pi* S, in 194 asbestos workers, of whom 100 were asbestosis cases, and 94 were controls without disease (exposed controls, EC). A second group of controls without asbestos exposure (non-exposed controls, NEC; n=122) was also included. Multivariate analysis adjusted by age and smoking habit showed ninefold risk for asbestosis in Pi*Z heterozygous individuals and 5.9-fold risk for Pi*S homozygous although differences were only significant in the first case (cases vs. EC: OR 8.9; p=0.04). Considering both genotypes (Pi*Z heterozygous, Pi*S homozygous) we obtained an OR of 8 (p=0.01). Our results suggest that the alpha 1 antitrypsin polymorphisms, especially Pi*Z, could help to predict asbestosis risk and confirm the high prevalence of the Pi*S allele in Spain.

In plain English

This Spanish case-control study asked whether two inherited alpha 1 antitrypsin gene variants, Pi*Z and Pi*S, were linked to asbestosis. The authors tested DNA from 194 highly exposed asbestos workers recruited through a regional workplace-safety agency in Barcelona. Of these, 100 had asbestosis diagnosed from chest X-rays and 94 were exposed workers without disease. They also tested 122 hospital patients with no occupational exposure to fibers to describe the local population. The workers came from cement, friction-material, asbestos-textile, shipyard and fiber-handling industries. One copy of Pi*Z was found in 7 of 100 cases and 1 of 94 exposed controls. After adjusting for age and smoking, the odds ratio for asbestosis was 8.9 (confidence interval 1.02 to 76.4) for one Pi*Z copy. For two Pi*S copies it was 5.9 (0.62 to 56.4), which was not statistically significant. Grouping workers with either genotype against all other workers gave 8.0 (1.63 to 39.1). The authors concluded that these variants, especially Pi*Z, could help predict asbestosis risk. They noted that fiber measurements existed only for whole work areas and only since 1980.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case-control genetic susceptibility study (asbestosis cases vs. exposed workers without disease, plus a non-exposed reference group)
• Who was studied: 194 active or retired asbestos workers recruited through the Center for Safety and Health Conditions at Work (Barcelona, Spain): 100 with asbestosis (diagnosed by chest X-ray, ILO classification) and 94 exposed workers without disease. A reference group of 122 hospital trauma patients in Barcelona with no occupational fiber exposure was also tested (the methods section says 121).
• Exposure: Occupational asbestos exposure in cement production, friction materials production and repair, asbestos textiles, shipyards and stevedoring, and asbestos fiber handling. Exposure was scored by a job-exposure matrix combining intensity and duration into low, medium and high categories. Fiber types were not specified. High exposure applied to 74 of 97 cases and 67 of 88 exposed controls.
• Main results:
  • One copy of Pi*Z (MZ genotype) was found in 7 of 100 cases (7%), 1 of 94 exposed controls (1%) and 3 of 122 non-exposed controls (2.4%). No one in any group had two copies (ZZ).
  • Adjusted for age and smoking, one Pi*Z copy was associated with an odds ratio for asbestosis of 8.9 (confidence interval 1.02 to 76.4, p 0.04) in cases vs. exposed controls. Two Pi*S copies (SS genotype: 4 of 100 cases, 1 of 94 exposed controls) gave an odds ratio of 5.9 (0.62 to 56.4, p 0.1), which was not statistically significant.
  • Workers with either one Pi*Z copy or two Pi*S copies, compared with all others, had an adjusted odds ratio of 8.0 (confidence interval 1.63 to 39.1, p 0.01).
  • In the non-exposed reference group, 18.8% carried one Pi*S copy and 0.8% two copies. The Pi*S allele frequency was 10.2% and the Pi*Z allele frequency 1.2%.
• The authors' conclusion: The authors concluded that alpha 1 antitrypsin variants, especially Pi*Z, could help to predict asbestosis risk, and that the Pi*S allele might contribute in a minor way. They said the findings confirm the high prevalence of the Pi*S allele in Spain.
• Limitations the authors state:
  • Measured fiber concentrations were available only for areas of industrial activity, not individual workplaces, and only from 1980 onward.
  • The risk linked to two Pi*Z copies (ZZ) or the SZ combination could not be assessed because no participant had these genotypes.
  • Because asbestosis progresses, some workers now counted as controls could become cases in later years.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Occupational Exposure, Alveoli, Asbestos Exposure, Multivariate Analysis, Habit.

Related studies

• Pulmonary elastic recoil and diffusing capacity in subjects with intermediate concentrations of alpha-1 antitrypsin — A.W. Musk, P.W. Robertson (1976)
• Manganese and extracellular superoxide dismutase polymorphisms and risk for asbestosis — A. Franko, M. Dodic-Fikfak, et al. (2009)
• Radiographic changes and lung function in relation to activity of the glutathione transferases theta and mu among asbestos cement workers — K. Jakobsson, A. Rannug, et al. (1995)
• Inducible nitric oxide synthase genetic polymorphism and risk of asbestosis — A. Franko, M. Dodič-Fikfak, et al. (2011)
• Heme oxygenase-1 promoter polymorphism is associated with risk of malignant mesothelioma — A. Murakami, Y. Fujimori, et al. (2012)
• Tumour necrosis factor-alpha gene polymorphisms in asbestos-induced diseases — S. Helmig, N. Aliahmadi, et al. (2010)

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