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The GSTP1 Ile105 Val polymorphism modifies the metabolism of toluene di-isocyanate.

Broberg Palmgren, Karin LU ; Warholm, Margareta; Tinnerberg, Håkan LU ; Axmon, Anna LU ; Jönsson, Bo A LU ; Sennbro, Carl Johan LU ; Littorin, Margareta LU and Rannug, Agneta (2010) In Pharmacogenetics & Genomics 20(2). p.104-111
Abstract
BACKGROUND: Toluene di-isocyanate (TDI) is widely used in the production of polyurethane foams and paints. As TDI causes respiratory disease in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Polymorphisms in TDI metabolising genes may affect elimination kinetics, resulting in differences in body retention, and in its turn differences in adverse effects. OBJECTIVES: To analyze how genotype modifies the associations between (i) TDI in air (2,4-TDI and 2,6-TDI) and its metabolites toluene diamine (TDA; 2,4-TDA and 2,6-TDA) in hydrolyzed urine; and (ii) 2,4-TDA and 2,6-TDA in hydrolyzed plasma and 2,4-TDA and 2,6-TDA in urine. METHODS: Workers exposed to TDI were analyzed for 2,4-TDI and... (More)
BACKGROUND: Toluene di-isocyanate (TDI) is widely used in the production of polyurethane foams and paints. As TDI causes respiratory disease in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Polymorphisms in TDI metabolising genes may affect elimination kinetics, resulting in differences in body retention, and in its turn differences in adverse effects. OBJECTIVES: To analyze how genotype modifies the associations between (i) TDI in air (2,4-TDI and 2,6-TDI) and its metabolites toluene diamine (TDA; 2,4-TDA and 2,6-TDA) in hydrolyzed urine; and (ii) 2,4-TDA and 2,6-TDA in hydrolyzed plasma and 2,4-TDA and 2,6-TDA in urine. METHODS: Workers exposed to TDI were analyzed for 2,4-TDI and 2,6-TDI in air (N=70), 2,4-TDA and 2,6-TDA in hydrolyzed urine (N=124) and in plasma (N=128), and genotype: CYP1A1*2A, CYP1A1*2B, GSTA1-52, GSTM1O, GSTM3B, GSTP1 I105V, GSTP1 A114V, GSTT1O, MPO-463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, and SULT1A1 R213H. RESULTS: GSTP1 105 strongly modified the relationship between 2,4-TDA in plasma and in urine: ValVal carriers had about twice as steep regression slope than IleIle carriers. A similar pattern was found for 2,6-TDA. CYP1A1*2A, GSTM1, GSTP1, GSTT1, and MPO possibly influenced the relationship between TDA in plasma and urine. CONCLUSION: Our results show, for the first time, genetic modification on the human TDI metabolism. The findings suggest that GSTP1 genotype should be considered when evaluating biomarkers of TDI exposure in urine and plasma. Moreover, the results support earlier findings of GSTP1 105 Val as protective against TDI-related asthma. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pharmacogenetics & Genomics
volume
20
issue
2
pages
104 - 111
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000274306700005
  • pmid:20032816
  • scopus:75649113766
ISSN
1744-6872
DOI
10.1097/FPC.0b013e328334fb84
language
English
LU publication?
yes
id
02a97f95-9963-4092-a253-2f353233283f (old id 1523338)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20032816?dopt=Abstract
date added to LUP
2010-01-11 14:39:47
date last changed
2018-05-29 10:32:01
@article{02a97f95-9963-4092-a253-2f353233283f,
  abstract     = {BACKGROUND: Toluene di-isocyanate (TDI) is widely used in the production of polyurethane foams and paints. As TDI causes respiratory disease in only a fraction of exposed workers, genetic factors may play a key role in disease susceptibility. Polymorphisms in TDI metabolising genes may affect elimination kinetics, resulting in differences in body retention, and in its turn differences in adverse effects. OBJECTIVES: To analyze how genotype modifies the associations between (i) TDI in air (2,4-TDI and 2,6-TDI) and its metabolites toluene diamine (TDA; 2,4-TDA and 2,6-TDA) in hydrolyzed urine; and (ii) 2,4-TDA and 2,6-TDA in hydrolyzed plasma and 2,4-TDA and 2,6-TDA in urine. METHODS: Workers exposed to TDI were analyzed for 2,4-TDI and 2,6-TDI in air (N=70), 2,4-TDA and 2,6-TDA in hydrolyzed urine (N=124) and in plasma (N=128), and genotype: CYP1A1*2A, CYP1A1*2B, GSTA1-52, GSTM1O, GSTM3B, GSTP1 I105V, GSTP1 A114V, GSTT1O, MPO-463, NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, and SULT1A1 R213H. RESULTS: GSTP1 105 strongly modified the relationship between 2,4-TDA in plasma and in urine: ValVal carriers had about twice as steep regression slope than IleIle carriers. A similar pattern was found for 2,6-TDA. CYP1A1*2A, GSTM1, GSTP1, GSTT1, and MPO possibly influenced the relationship between TDA in plasma and urine. CONCLUSION: Our results show, for the first time, genetic modification on the human TDI metabolism. The findings suggest that GSTP1 genotype should be considered when evaluating biomarkers of TDI exposure in urine and plasma. Moreover, the results support earlier findings of GSTP1 105 Val as protective against TDI-related asthma.},
  author       = {Broberg Palmgren, Karin and Warholm, Margareta and Tinnerberg, Håkan and Axmon, Anna and Jönsson, Bo A and Sennbro, Carl Johan and Littorin, Margareta and Rannug, Agneta},
  issn         = {1744-6872},
  language     = {eng},
  number       = {2},
  pages        = {104--111},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Pharmacogenetics & Genomics},
  title        = {The GSTP1 Ile105 Val polymorphism modifies the metabolism of toluene di-isocyanate.},
  url          = {http://dx.doi.org/10.1097/FPC.0b013e328334fb84},
  volume       = {20},
  year         = {2010},
}