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

被引:35
作者
Schnakenberg, Eckart
Fabig, Karl-Rainer
Stanulla, Martin
Strobl, Nils
Lustig, Michael
Fabig, Nathalie
Schloot, Werner
机构
[1] Inst Pharmacogenet & Genet Disposit, D-30853 Langenhagen, Germany
[2] Clin Practice Toxicol & Environm Med, D-22417 Hamburg, Germany
[3] Univ Bremen, Ctr Human Genet & Genet Counseling, D-28359 Bremen, Germany
[4] Hannover Med Sch, Childrens Hosp, D-30625 Hannover, Germany
关键词
D O I
10.1186/1476-069X-6-6
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Background: 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. Methods: 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. Results: 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. Conclusion: 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.
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页数:10
相关论文
共 45 条
[1]  
AliOsman F, 1997, J BIOL CHEM, V272, P10004
[2]   Genetic polymorphisms in human xenobiotica metabolizing enzymes as susceptibility factors in toxic response [J].
Autrup, H .
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2000, 464 (01) :65-76
[3]   Influence of GSTM1 and GSTT1 genotypes on sister chromatid exchange induction by styrene in cultured human lymphocytes [J].
Bernardini, S ;
Hirvonen, A ;
Järventaus, H ;
Norppa, H .
CARCINOGENESIS, 2002, 23 (05) :893-897
[4]   N-acetyltransferase 2 polymorphism in sporadic Parkinson's disease in a Polish population [J].
Bialecka, M ;
Gawronska-Szklarz, B ;
Drozdzik, M ;
Honczarenko, K ;
Stankiewicz, J .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2002, 57 (12) :857-862
[5]   MOLECULAR MECHANISM OF SLOW ACETYLATION OF DRUGS AND CARCINOGENS IN HUMANS [J].
BLUM, M ;
DEMIERRE, A ;
GRANT, DM ;
HEIM, M ;
MEYER, UA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (12) :5237-5241
[6]   Relationship between metabolic enzyme polymorphism and colorectal cancer [J].
Chen, Kun ;
Jiang, Qin-Ting ;
He, Han-Qing .
WORLD JOURNAL OF GASTROENTEROLOGY, 2005, 11 (03) :331-335
[7]  
CULLEN MR, 1987, OCCUP MED, V2, P655
[8]  
de Jong MM, 2002, CANCER EPIDEM BIOMAR, V11, P1332
[9]   Glutathione S-transferase polymorphisms influence the level of oxidative DNA damage and antioxidant protection in humans [J].
Dusinská, M ;
Ficek, A ;
Horská, A ;
Raslová, K ;
Petrovská, H ;
Vallová, B ;
Drlicková, M ;
Wood, SG ;
Stupáková, A ;
Gasparovic, J ;
Bobek, P ;
Nagyová, A ;
Kováciková, Z ;
Blazícek, P ;
Liegebel, U ;
Collins, AR .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2001, 482 (1-2) :47-55
[10]   Aromatic DNA adducts and polymorphisms of CYP1A1, NAT2, and GSTM1 in breast cancer [J].
Firozi, PF ;
Bondy, ML ;
Sahin, AA ;
Chang, P ;
Lukmanji, F ;
Singletary, ES ;
Hassan, MM ;
Li, DH .
CARCINOGENESIS, 2002, 23 (02) :301-306