Genetic susceptibility in solvent induced neurobehavioral effects.

The aim of this investigation was to study the influence of genetic polymorphisms of biotransformation enzymes and dopamine receptors on neurobehavioral effects in referents (n = 53), solvent-workers (n = 144), and chronic toxic encephalopathy (CTE) patients (n = 33). All participants were interviewed for exposure data and confounding factors and underwent a clinical examination. Neurobehavioral complaints (neurotoxicity symptom checklist-60) and effects [simple reaction time (SRT), symbol digit substitution (SDS), hand-eye coordination (HEC), and digit span backwards (DSB)] were evaluated with a computer assisted test battery. The following genotypes were determined: GSTM1, GSTT1, GSTP1, DRD2 Taq1A, DRD2 Taq1B, and DRD2-141Cdel. Neurotoxic effects and complaints were significantly higher in CTE patients and were related to both duration and level of exposure. An equal distribution of genotypes was found between all groups. Logistic regression analysis revealed that GSTT1 was negatively associated with sleep and sensorimotor complaints. GSTM1 had a protecting influence on the relationship between logDSB and the cumulative exposure index and between logSRT and cumulative exposure index and degree of exposure, respectively. This effect was also found when correcting for age, education level, alcohol consumption, and smoking. DRD2-141Cdel polymorphisms had a negative influence on the relationship between logSDS and the total exposure time. GSTT1 might be protective against sleep and sensorimotor complaints, whereas GSTM1 seems to decrease sustained attention and short-term memory problems in relation to solvent exposure. Individuals possessing DRD2-141Cdel variant experienced more visuomotor problems.