Global DNA hypomethylation has no impact on lung function or serum inflammatory and fibrosis cytokines in asbestos-exposed population

Our plain-English summary of Global DNA hypomethylation has no impact on lung function or serum inflammatory and fibrosis cytokines in asbestos-exposed population, by M. Yu, J. Lou, H. Xia, et al (International Archives of Occupational and Environmental Health, 2017).

The study

• Authors: M. Yu, J. Lou, H. Xia, M. Zhang, Y. Zhang, J. Chen, X. Zhang, S. Ying, L. Zhu, L. Liu, G. Jia
• Journal: International Archives of Occupational and Environmental Health
• Published: 2017;90(3):265-274
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: To examine the effect of asbestos exposure on global DNA methylation and determine whether lung function and inflammatory and fibrosis biomarkers are correlated with the methylation state.

Methods: A total of 26 healthy subjects without asbestos exposure (Group 1), 47 healthy subjects with exposure (Group 2), and 52 subjects with benign asbestos-related disorders (ARDs) (Group 3) participated in this cross-sectional study. Blood global 5-methylcytosine (5mC) and serum TNF-α, collagen IV, CCL5 and CC16 concentrations were analyzed using enzyme-linked immunosorbent assay-like assays. Spirometric maneuvers were performed to assess lung function.

Results: Decreased 5mC levels were observed in Groups 2 and 3 compared to Group 1, irrespective of lung function (p < 0.01). There was no significant change in 5mC between Groups 2 and 3. Overall, 5mC was negatively correlated with CCL5 and collagen IV (p < 0.05), but no significant inverse relationship was found between 5mC and CCL5 or collagen IV in each group. Additionally, both 5mC and CC16 were inversely associated with FEV1/FVC% (p = 0.001, adjusted R 2 = 0.145) for non-smokers, and consistently significant inverse relationships were found between CC16 and FEV1/FVC%, independent of asbestos exposure.

Conclusions: Asbestos exposure causes global DNA hypomethylation. DNA hypomethylation has no influence on serum biomarkers and lung function in asbestos-exposed population with or without pleural and pulmonary parenchymal abnormalities.

In plain English

This cross-sectional study asked whether asbestos exposure was linked to lower overall DNA methylation in blood (measured as 5-methylcytosine, or 5mC), and whether methylation was related to lung function and blood markers of inflammation and fibrosis. There were 125 participants, all residents of towns that had plants making asbestos-related products. Twenty-six were healthy and unexposed, 47 were apparently healthy people occupationally exposed to asbestos, and 52 had asbestosis or pleural plaques. The article does not name the fiber type. Median 5mC was 1.22% in the unexposed group, 0.61% in the exposed healthy group and 0.57% in the asbestosis and pleural plaque group. Within each group, 5mC did not differ statistically significantly between people with and without a ventilation disorder on spirometry. It was not related to years of exposure or estimated exposure level. Across all participants, higher 5mC went with lower CCL5 and collagen IV, but the within-group comparisons were not statistically significant. The authors concluded that global DNA methylation was low in the blood of asbestos-exposed workers, and that this may not affect lung function or the serum markers. They noted that they measured only global methylation, not gene-specific methylation.

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: cross-sectional study
• Who was studied: 125 residents (out of 262 invited) of towns with plants that formerly manufactured asbestos-related products. Group 1: 26 healthy people without asbestos exposure. Group 2: 47 apparently healthy people occupationally exposed to asbestos. Group 3: 52 people with asbestosis or pleural plaques. Group 1 was mostly male (22/4) and 50% smokers; Groups 2 and 3 were mostly female. The towns' location and the study dates are not stated in the text; the authors' institutions are in Beijing and Zhejiang, China.
• Exposure: Former occupational asbestos exposure in asbestos-product manufacturing (described in the discussion as household textile workshops); fiber type not stated. Median exposure time was 6.5 years (Group 2) and 10.0 years (Group 3). Median potential exposure level was 11.2 (Group 2) and 17.7 (Group 3) mg/m3 times years.
• Main results:
  • Median blood 5mC was 1.22% in Group 1 (n=24), 0.61% in Group 2 (n=42) and 0.57% in Group 3 (n=46). Groups 2 and 3 were lower than Group 1 (p less than 0.001).
  • The 5mC differences between groups remained significant after adjustment for gender and smoking.
  • Within each group, 5mC did not differ significantly between subjects with and without a ventilation disorder.
  • 5mC was not related to years of exposure or to estimated exposure level.
  • Across all participants, 5mC was inversely associated with CCL5 (minus 0.260, p = 0.011) and collagen IV (minus 0.215, p = 0.038), after adjustment for age, gender, smoking, ventilation disorder and creatinine.
  • Within each group, CCL5 and collagen IV appeared lower in subjects with higher 5mC than in those with lower 5mC, but these differences were not statistically significant.
  • After adjustment for smoking, gender and creatinine, estimated mean CCL5 was 113.7 ng/ml in Group 1 and 157.1 ng/ml in Group 3; the difference was not statistically significant (p = 0.119).
  • Rates of any ventilation disorder were 36% (9/25) in Group 1, 40% (18/45) in Group 2 and 43.7% (21/48) in Group 3, with no significant differences among the groups.
  • In non-smokers, both 5mC (minus 0.242, p = 0.019) and CC16 (minus 0.351, p = 0.001) were inversely related to the FEV1/FVC% ratio.
  • After adjustment for age, gender, smoking, creatinine, 5mC and BMI, CC16 remained inversely correlated with FEV1/FVC% (minus 0.260, p = 0.010).
• The authors' conclusion: The authors concluded that global DNA methylation was low in the peripheral blood of asbestos-exposed workers. They also concluded that this hypomethylation may not modify lung function or serum inflammatory and fibrosis biomarkers in this population, with or without pleural or lung abnormalities. The abstract states this more strongly, saying that asbestos exposure causes global DNA hypomethylation.
• Limitations the authors state:
  • Only global DNA methylation was measured; the findings may not apply to gene-specific methylation.
  • Blood DNA methylation may not reflect specific tissues or organs and may be affected by other environmental exposures.
  • The immunoenzymatic assay used to measure methylation may have sensitivity issues.
  • More sensitive ELISA kits might detect slight changes in the serum biomarkers that these assays missed.

Topics

Medical terms in this study, explained in our Lexicon: Fibrosis, Cytokine, Asbestos Exposure, Biomarker, Collagen, FEV1/FVC Ratio.

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