A cross-sectional study of self-reported chemical-related sensitivity is associated with gene variants of drug-metabolizing enzymes

• Main Authors: Fabig Nathalie, Lustig Michael, Strobl Nils, Stanulla Martin, Fabig Karl-Rainer, Schnakenberg Eckart, Schloot Werner
• Format: Article
• Language: English
• Published: BMC 2007-02-01
• Series: Environmental Health
• Online Access: http://www.ehjournal.net/content/6/1/6

<p>Abstract</p> <p>Background</p> <p>N-acetyltransferases (NAT) and glutathione S-transferases (GST) are involved in the metabolism of several ubiquitous chemical substances leading to the activation and detoxification of carcinogenic heterocyclic and aromatic amines. Since polymorphisms within these genes are described to influence the metabolism of ubiquitous chemicals, we conducted the present study to determine if individuals with self-reported chemical-related sensitivity differed from controls without self-reported chemical-related sensitivity with regard to the distribution of genotype frequencies of <it>NAT2</it>, <it>GSTM1</it>, <it>GSTT1</it>, and <it>GSTP1 </it>polymorphisms.</p> <p>Methods</p> <p>Out of 800 subjects who answered a questionnaire of ten items with regard to their severity of chemical sensitivity 521 unrelated individuals agreed to participate in the study. Subsequently, genetic variants of the <it>NAT2</it>, <it>GSTM1</it>, <it>GSTT1</it>, and <it>GSTP1 </it>genes were analyzed.</p> <p>Results</p> <p>The results show significant differences between individuals with and without self-reported chemical-related sensitivity with regard to the distribution of <it>NAT2</it>, <it>GSTM1</it>, and <it>GSTT1 </it>gene variants. Cases with self-reported chemical-related sensitivity were significantly more frequently <it>NAT2 </it>slow acetylators (controlled OR = 1.81, 95% CI = 1.27–2.59, <it>P </it>= 0.001). <it>GSTM1 </it>and <it>GSTT1 </it>genes were significantly more often homozygously deleted in those individuals reporting sensitivity to chemicals compared to controls (<it>GSTM1</it>: controlled OR 2.08, 95% CI = 1.46–2.96, <it>P </it>= 0.0001; <it>GSTT1</it>: controlled OR = 2.80, 95% CI = 1.65–4.75, <it>P </it>= 0.0001). Effects for <it>GSTP1 </it>gene variants were observed in conjunction with <it>GSTM1, GSTT1 </it>and <it>NAT2 </it>gene.</p> <p>Conclusion</p> <p>The results from our study population show that individuals being slow acetylators and/or harbouring a homozygous <it>GSTM1 </it>and/or <it>GSTT1 </it>deletion reported chemical-related hypersensitivity more frequently.</p>