Schnakenberg Eckart, Fabig Karl-Rainer, Stanulla Martin, Strobl Nils, Lustig Michael, Fabig Nathalie, Schloot Werner
Institute for Pharmacogenetic and Genetic Disposition, Ostpassage 7, D-30853 Langenhagen, Germany.
Environ Health. 2007 Feb 10;6:6. doi: 10.1186/1476-069X-6-6.
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 NAT2, GSTM1, GSTT1, and GSTP1 polymorphisms.
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 NAT2, GSTM1, GSTT1, and GSTP1 genes were analyzed.
The results show significant differences between individuals with and without self-reported chemical-related sensitivity with regard to the distribution of NAT2, GSTM1, and GSTT1 gene variants. Cases with self-reported chemical-related sensitivity were significantly more frequently NAT2 slow acetylators (controlled OR = 1.81, 95% CI = 1.27-2.59, P = 0.001). GSTM1 and GSTT1 genes were significantly more often homozygously deleted in those individuals reporting sensitivity to chemicals compared to controls (GSTM1: controlled OR 2.08, 95% CI = 1.46-2.96, P = 0.0001; GSTT1: controlled OR = 2.80, 95% CI = 1.65-4.75, P = 0.0001). Effects for GSTP1 gene variants were observed in conjunction with GSTM1, GSTT1 and NAT2 gene.
The results from our study population show that individuals being slow acetylators and/or harbouring a homozygous GSTM1 and/or GSTT1 deletion reported chemical-related hypersensitivity more frequently.
N - 乙酰转移酶（NAT）和谷胱甘肽S - 转移酶（GST）参与多种普遍存在的化学物质的代谢，导致致癌性杂环胺和芳香胺的活化与解毒。由于这些基因内的多态性被认为会影响普遍存在的化学物质的代谢，我们开展了本研究，以确定自我报告有化学物质相关敏感性的个体与无自我报告化学物质相关敏感性的对照个体在NAT2、GSTM1、GSTT1和GSTP1基因多态性的基因型频率分布上是否存在差异。
在800名回答了关于其化学敏感性严重程度的十项问卷的受试者中，521名无亲缘关系的个体同意参与研究。随后，对NAT2、GSTM1、GSTT1和GSTP1基因的遗传变异进行了分析。
结果显示，自我报告有化学物质相关敏感性的个体与无自我报告化学物质相关敏感性的个体在NAT2、GSTM1和GSTT1基因变异的分布上存在显著差异。自我报告有化学物质相关敏感性的病例中，NAT2慢乙酰化者的比例显著更高（校正后的比值比=1.81，95%置信区间=1.27 - 2.59，P = 0.001）。与对照组相比，报告对化学物质敏感的个体中，GSTM1和GSTT1基因纯合缺失的情况显著更常见（GSTM1：校正后的比值比2.08，95%置信区间=1.46 - 2.96，P = 0.0001；GSTT1：校正后的比值比=2.80，95%置信区间=1.65 - 4.75，P = 0.0001）。在GSTM1、GSTT1和NAT2基因的共同作用下观察到了GSTP1基因变异的影响。
我们研究人群的结果表明，慢乙酰化者和/或携带GSTM1和/或GSTT1基因纯合缺失的个体更频繁地报告有化学物质相关的超敏反应。
