Meny

Javascript verkar inte påslaget? - Vissa delar av Lunds universitets webbplats fungerar inte optimalt utan javascript, kontrollera din webbläsares inställningar.
Du är här

Influence of polymorphic metabolic enzymes on biotransformation and effects of diphenylmethane diisocyanate.

Författare:
Publiceringsår: 2008
Språk: Engelska
Sidor: 429-441
Publikation/Tidskrift/Serie: International Archives of Occupational and Environmental Health
Volym: 81
Nummer: 4
Dokumenttyp: Artikel
Förlag: Springer Berlin / Heidelberg

Sammanfattning

Objectives To identify effect modification produced by genetic traits found in metabolic enzymes, to investigate how these affect the levels of different biomarkers of sprayed and thermo-degraded polyurethane (PUR) based on 4,4′-diphenylmethane diisocyanate (MDI) and to determine how associated respiratory disorders are affected.
Methods Two partly overlapping groups of 141 and 158 factory employees exposed to sprayed or heated MDI-PUR glue were examined in years 0 and 2, respectively, for occurrence of polymorphisms in five genes (N-acetyltransferase NAT2 and the glutathione S-transferases GSTM1, GSTM3, GSTP1 [codon 105 and 114] and GSTT1) on the basis of the polymerase chain reaction, exposure biomarkers in plasma and urine (P- and U-MDX), by means of gas chromatography-mass spectrometry, specific serum IgG antibodies against MDI (S-IgG-MDI) by means of ELISA, total S-IgE, symptoms in the eyes, nose and lower airways as assessed by questionnaire and interview, and lung function as measured by spirometry.
Results Both the GSTP1 105 isoleucine/isoleucine and GSTP1 114 alanine/alanine genotypes showed higher levels of U-MDX than the other genotypes and the GSTP1 114 genotype modified the P-MDX/U-MDX relationship. GSTP1 105 isoleucine/isoleucine was found to be associated with lower levels of S-IgG-MDI and fewer eye symptoms, but with an increased risk of symptoms in the airways, as well as with atopy. Presence of the GSTT1 gene resulted in somewhat lower lung function levels than did the null genotype. A slow NAT2 acetylating capacity was associated with lower P- and U-MDX and S-IgG-MDI levels, and better lung function, but a higher risk of eye and airway symptoms. Analysing the effects of combinations of the different genes provided no further information.
Conclusions Although our study has clear limitations, it reveals various effect modifications produced by the GST and NAT2 genotypes. Gene-environment interactions are highly complex. Further research is needed to obtain a more comprehensive understanding of them.

Disputation

Nyckelord

  • Medicine and Health Sciences

Övriga

Published
Yes
  • ISSN: 0340-0131

Box 117, 221 00 LUND
Telefon 046-222 00 00 (växel)
Telefax 046-222 47 20
lu [at] lu [dot] se

Fakturaadress: Box 188, 221 00 LUND
Organisationsnummer: 202100-3211
Om webbplatsen