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Interaction between smoking and glutathione S-transferase polymorphisms in solvent-induced chronic toxic encephalopathy
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för molekylär och klinisk medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
2002 (engelsk)Inngår i: Toxicology and industrial health, ISSN 0748-2337, E-ISSN 1477-0393, Vol. 18, nr 6, s. 289-296Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Exposure to organic solvents is still common in industrial and other work environments, and increases the risk of chronic toxic encephalopathy (CTE). Genetic variation in metabolic enzymes for solvents and other xenobiotics may modify the risk of developing toxic effects. Therefore, we investigated the presence of null genotypes for glutathione S-transferases M1 and T1 (GSTM1, GSTT1) and two genetic polymorphisms of microsomal epoxide hydrolase (mEPHX) in relation to the risk for chronic toxic encephalopathy (CTE) when exposed to solvents and smoking. We genotyped 115 patients who were classified into three categories: CTE (n = 56), incipient CTE (n = 27) and non-CTE (n = 32) patients. DNA was isolated from leucocytes and the GSTM 1 and GSTT1 null genotypes were determined by multiplex-polymerase chain reaction. The two polymorphisms of mEPHX were analysed by PCR-RFLP (restriction fragment length polymorphism) based assays. All analyses were performed blindly with regard to both exposure and disease status. An increased binomial regression risk ratio = 2.5, 95% confidence interval (CI) 1.5-4.2, of the GSTM1 null genotype for CTE was found in smokers and for the GSTT1 null genotype (binomial regression risk ratio 1.5, 95% CI 1.0-2.0). In nonsmokers, the GSTM1 null genotype did not confer any risk for CTE. None of the studied mEPHX polymorphisms were associated with an increased risk for CTE. We suggest that the GSTM1 null genotype in smokers is a possible risk for solvent-induced CTE.

sted, utgiver, år, opplag, sider
2002. Vol. 18, nr 6, s. 289-296
Emneord [en]
chronic toxic encephalopathy, molecular epidemiology, polymorphism, smoking, solvent exposure
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-46280DOI: 10.1191/0748233702th152oaOAI: oai:DiVA.org:liu-46280DiVA, id: diva2:267176
Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2017-12-13bibliografisk kontrollert
Inngår i avhandling
1. Genetic predisposition and risk factors for neurodegenerative diseases
Åpne denne publikasjonen i ny fane eller vindu >>Genetic predisposition and risk factors for neurodegenerative diseases
2004 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

The inter-individual variability in biotransformation, may lead to differences in activation and detoxification of both endogenous and exogenous compounds. Polymorphism studies in such genes were applied for Parkinson's disease (PD) and Chronic toxic encephalopathy (CTE), two diseases influenced by both genetic and enviromnental factors.

An elevated median age for the onset of PD was found among GS1M1 gene carriers compared to PD patients being GS1M1 null genotypes (68 years versus 57 years). No similar difference was found for GSTT1. mEPHX (113HH) isoform, which has been suggested as a low activity variant, is over represented in PD patients (OR=3.8, CI 95%, 1.2-11.8).

Monoamine oxidases (MAO-A and -B) are important in the dopamine metabolism and in the detoxification of neurotoxins and genetic variants in these genes have earlier been assigned to PD. However, no difference was revealed between any of the polymorphisms studied in the MAO-A and -B genes and PD. Smoking displayed an enviromnental exposure with a strong decreased risk for PD in this study (OR=0.40 for men and OR=0.48 for women) but no obvious interaction with the MAO genotypes could be observed.

Mitochondrial dysfunction and oxidative stress have been hypothesized to contribute to the pathogenesis of PD. The superoxide dismutases (SOD) potentially play an important role in PD by detoxifying superoxide radicals in mitochondria. Polymorphisms neither in superoxide dismutase 2 (SOD2) nor mitochondrial complex I subunit, NDUFV2, were associated with PD.

An increased risk ratio for CTE was found in smokers with the GSTM1 null genotype (RR=2.5, Cl 95%, 1.4-4.2) or the GSTT1 null genotype (RR=1.4, Ci 95%, 1.02-2.0). In non-smokers GS1M1 null genotype did not confer any risk for CTE. Polymorphisms in mEPHX were not associated with an increased risk for CTE.

Thus, various genetic and enviromnental factors most likely influence both PD and solvent-induced CTE. Detoxification pathways may represent important protective mechanisms against reactive intermediates, thus genetic predisposition in these pathways could modify the susceptibility and onset of PD and solvent-induced CTE.

sted, utgiver, år, opplag, sider
Linköping: Linköpings universitet, 2004. s. 63
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 844
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-24042 (URN)3598 (Lokal ID)91-7373-817-4 (ISBN)3598 (Arkivnummer)3598 (OAI)
Disputas
2004-04-16, Elsa Brändström-Salen, Hälsouniversitetet, Linköping, 09:00 (svensk)
Opponent
Tilgjengelig fra: 2009-10-07 Laget: 2009-10-07 Sist oppdatert: 2012-10-22bibliografisk kontrollert

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