The influence of genetic polymorphisms of GSTP1 on the development of asbestosis

Our plain-English summary of The influence of genetic polymorphisms of GSTP1 on the development of asbestosis, by A. Franko, V. Dolzan, N. Arnerić, et al (Journal of Occupational and Environmental Medicine, 2008).

The study

• Authors: A. Franko, V. Dolzan, N. Arnerić, M. Dodic-Fikfak
• Journal: Journal of Occupational and Environmental Medicine
• Published: 2008;50(1):7-12
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: Genetic factors play an important role in the development of asbestosis. The aim of this study was to investigate whether genetic polymorphisms of glutathione S-transferase (GST) P1 represent a risk factor for this disease.

Methods: The study population included 262 workers with asbestosis and 265 matched controls. Information on cumulative asbestos exposure was available. A real-time PCR based on the 5' nuclease assay was designed for the analysis of GSTP1 Ile105Val and Ala114Val polymorphisms.

Results: Asbestosis was associated with GSTP1 genotype coding for an enzyme with high conjugation capacity versus genotypes resulting in intermediate and low enzyme activity (odds ratio = 1.49, confidence interval = 1.06-2.10).

Conclusions: The key finding of the study was that GSTP1 genotype coding for an enzyme with high conjugation capacity significantly increases the risk of developing asbestosis.

In plain English

This Slovenian study asked whether inherited variants of the GSTP1 gene were linked to asbestosis. It was a nested case-control study within 2080 asbestos-exposed workers seen by an occupational asbestos disease board from 1998 to 2003. It compared 262 workers with asbestosis with 265 workers with no asbestos-related disease. Controls were selected to match cases by gender and age, but among participants the mean age was 61 for cases and 57 for controls, a significant difference. Cases had higher average cumulative asbestos exposure than controls. About 45% of each group were ever smokers. The genotype presumed to give the highest enzyme activity (*A/*A) was found in 52.5% of cases and 42.6% of controls. Compared with intermediate- and low-activity genotypes combined, this gave an odds ratio of 1.49 (95% confidence interval 1.06 to 2.10). After adjustment for cumulative exposure it was 1.36 (0.94 to 1.98), a range that included 1. The Ala114Val variant showed no association with asbestosis. The authors concluded that this genotype significantly increases the risk of asbestosis. They reported excluding 26% of selected subjects, who did not differ from participants in exposure.

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: nested case-control study within a cohort of asbestos-exposed workers
• Who was studied: The cohort was 2080 asbestos-exposed workers presented at the Board for the Recognition of Occupational Asbestos Diseases (Ljubljana, Slovenia) from January 1, 1998 to December 31, 2003. From it, 356 cases with asbestosis and 356 controls with no asbestos-related disease, matched by gender and age, were selected. After deaths, malignant disease and refusals, 262 cases (186 men, 76 women) and 265 controls (183 men, 82 women) took part. The mean age of the participating cases was 61 years and of the participating controls 57 years.
• Exposure: Occupational asbestos exposure, measured as cumulative exposure (fibers/cm3-years) and taken from a previous study. The article does not specify fiber types. The genetic factors studied were the GSTP1 Ile105Val and Ala114Val variants, grouped by presumed enzyme conjugation capacity.
• Main results:
  • Among participants, the mean age of cases (61 years) was significantly higher than that of controls (57 years), even though the controls had been selected to match the cases by age.
  • Average cumulative asbestos exposure was higher in cases (37.67 fibers/cm3-years) than in controls (11.23 fibers/cm3-years). Average exposure duration was 22.30 years for cases and 19.15 years for controls.
  • Smoking did not differ between cases and controls. About 45% of each group were ever smokers, and the odds ratio for smoking (ever/never) was 0.98 (CI 0.69–1.39).
  • The *A/*A genotype (high conjugation capacity) was found in 137 of 261 cases (52.5%) and 112 of 263 controls (42.6%).
  • For the high conjugation capacity genotype compared with the intermediate and low capacity genotypes together, the odds ratio of asbestosis was 1.49 (95% CI 1.06–2.10).
  • After adjustment for cumulative asbestos exposure, the odds ratio for the high conjugation capacity genotype was 1.36 (95% CI 0.94–1.98).
  • Compared with the low capacity genotypes alone, the odds ratio for the high capacity genotype was 1.50 (95% CI 0.81–2.80).
  • Analysed separately, the 105Ile/Ile genotype had an odds ratio of asbestosis of 1.52 (CI 1.08–2.15) compared with the 105Ile/Val and 105Val/Val genotypes together.
  • The Ala114Val variant was not associated with asbestosis. The odds ratio was 0.97 (CI 0.64–1.48) for 114Ala/Ala compared with the other genotypes.
• The authors' conclusion: The authors concluded that the GSTP1 genotype coding for an enzyme with high conjugation capacity (*A/*A) significantly increases the risk of developing asbestosis, by 50% in their words. They also concluded that the Ile105Val variant mainly accounts for this.
• Limitations the authors state:
  • 26% of the originally selected cases and controls were excluded because of death, malignant disease, or refusal. The authors reported no differences in cumulative exposure, duration of exposure, or cancer diagnosis between excluded subjects and participants.

Topics

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

Medical terms in this study, explained in our Lexicon: Glutathione (GSH), Asbestos Exposure, Odds Ratio, confidence interval.

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• Glutathione S-transferases GSTM1 and GSTT1 polymorphisms and asbestosis — A. Franko, M. Dodic-Fikfak, et al. (2007)
• Manganese and extracellular superoxide dismutase polymorphisms and risk for asbestosis — A. Franko, M. Dodic-Fikfak, et al. (2009)
• The role of polymorphisms in glutathione-related genes in asbestos-related diseases — A. Franko, K. Goricar, et al. (2021)
• The influence of gene-gene and gene-environment interactions on the risk of asbestosis — A. Franko, V. Dolžan, et al. (2013)

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