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GTn heme oxygenase-1 polymorphism in beryllium-exposed dental technicians

Moshe Stark, Yehuda Lerman, Lee Newman, Lisa Maier, Elizabeth Fireman
European Respiratory Journal 2012 40: P4026; DOI:
Moshe Stark
1Institute of Pulmonary Diseases, National Laboratory Service for ILD, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
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Yehuda Lerman
2Occupational Health Department, Clalit Medical Services, Tel-Aviv, Israel
3Department of Epidemiology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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Lee Newman
6Environmental Occupational Health Department,, University of Colorado, Aurora, Denver, United States
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Lisa Maier
5Division of Occupational Health Sciences, National Jewish Medical Center, Denver, United States
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Elizabeth Fireman
1Institute of Pulmonary Diseases, National Laboratory Service for ILD, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
4Department of Occupational and Environmental Medicine, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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Abstract

Background: Dental technicians (DTs) are exposed to Beryllium (Be) and other substances capable of inducing lung disease. Heme oxygenase -1 (HO-1) play a protective antioxidant role in the lung. The guanine-thymidine (GT) n repeats in the HO-1 promoter determine HO-1 induction level. Short (GT) n repeats (n = <25; S genotype) is considered as protective since HO-1 is induced more rapidly than in long (GT) n repeats (n = ≥25; L genotype).

Aims To evaluate the correlation of HO-1 polymorphisms to functional and exposure parameters in DTs and the protective role of HO-1 on Be Oxide (BeO) exposed A549 epithelial cells apoptosis.

Methods 65 DTs were followed-up for 2 years by questionnaires,induced sputum (IS) particles size distribution laser analysis (Dapi 2000 Donner Tech and Pulmonary Function Tests. HO-1 genotyping was done by PCR DNA sequencer (AB prism 310). A549 epithelial cell line was cultured with BeO and pretreated with Hemin and Znpp (for stimulation and inhibition of HO-1 respectively), HO-1 gene expression was evaluated in IS and A549 cells by quantitative PCR and apoptosis by TUNEL staining.

Results: Association was found between GTn and HO-1 gene expression in IS (r=-0.35 p=0.017), the GTn<25 group had higher HO1 expression than the GTn>25 group (0.18±0.16 Vs 0.07±0.06 p= 0.007 respectively). Decrease in DLCO (Diffusion Lung CO) was associate with GTn >25. Hemin increases the HO-1 gene expression and decreases the apoptosis levels in A549 epithelial cells while is increased by ZnPP.

Conclusions: DLCO decrease is associated with L genotype. Decrease apoptosis in BeO-exposed A549 epithelial cells by hemin may indicate a protective role of HO-1.

Supported by USA-Israel Bi National Science Foundation.

  • Occupation
  • Interstitial lung disease
  • Genetics
  • © 2012 ERS
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GTn heme oxygenase-1 polymorphism in beryllium-exposed dental technicians
Moshe Stark, Yehuda Lerman, Lee Newman, Lisa Maier, Elizabeth Fireman
European Respiratory Journal Sep 2012, 40 (Suppl 56) P4026;

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GTn heme oxygenase-1 polymorphism in beryllium-exposed dental technicians
Moshe Stark, Yehuda Lerman, Lee Newman, Lisa Maier, Elizabeth Fireman
European Respiratory Journal Sep 2012, 40 (Suppl 56) P4026;
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