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Genetic Susceptibility in Solvent Induced Neurobehavioral Effects

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Abstract

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.

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Abbreviations

CTE:

Chronic toxic encephalopathy

GST:

Glutathione S-transferase

CYP P450:

Cytochrome P450

EPHX1:

Microsomal epoxide hydrolase 1

DRD:

Dopamine D receptor

SRT:

Simple reaction time

SDS:

Symbol digit substitution

HEC:

Hand–eye coordination

DSB:

Digit span backwards

NSC-60:

Neurotoxicity symptom checklist-60

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Acknowledgments

Financial support for this study was provided by IDEWE, External Service for Prevention and Protection at work. We are grateful to Patrick Vercammen for his expert technical assistance.

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Authors and Affiliations

  1. Faculty of Medicine, Department of Occupational, Environmental and Insurance Medicine, Katholieke Universiteit Leuven, Kapucijnenvoer 35/5, Leuven, 3000, Belgium

    L. Godderis, G. Moens & M. K. Viaene

  2. IDEWE, External Service for Prevention and Protection at Work, Interleuvenlaan 58, Hevelee, 3000, Belgium

    L. Godderis, N. Maertens, S. Bulterys & G. Moens

  3. Faculty of Medicine, Department of Basic Medical Sciences, Ghent University, De Pintelaan 185, Ghent, 9000, Belgium

    V. de Gelder, K. De Ruyck & H. Thierens

  4. Johnson & Johnson, Turnhoutseweg 30, Beerse, 2340, Belgium

    A. De Lamper & M. Vernimmen

  5. Neuropsychotoxicological Expertise Center, Governmental Psychiatric Hospital, Pas 200, Geel, 2440, Belgium

    M. K. Viaene

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  1. L. Godderis
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  2. N. Maertens
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  3. V. de Gelder
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  7. S. Bulterys
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  8. G. Moens
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  9. H. Thierens
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  10. M. K. Viaene
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Correspondence to L. Godderis.

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Godderis, L., Maertens, N., de Gelder, V. et al. Genetic Susceptibility in Solvent Induced Neurobehavioral Effects. Neurotox Res 17, 268–278 (2010). https://doi.org/10.1007/s12640-009-9100-7

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  • DOI: https://doi.org/10.1007/s12640-009-9100-7

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