Possible influence of genetic polymorphism in the area of GSTs genes on the serum PCB level

Czech version

Authors: M. Tajtáková ¹; A. Pidaničová ²; M. Kmeťová‑ sivoňová ³; A. Kočan ⁴; B. Drobná ⁴; M. Javorský ⁵
Authors‘ workplace: Endokrinologická ambulancia Nemocnice Košice‑ Šaca, a. s., Slovenská republika, riaditeľ MU Dr. Juraj Vančík, CSc. ¹; I. interná klinika Lekárskej fakulty UPJŠ a UN L. Pasteura Košice, Slovenská republika, prednostka prof. MU Dr. Ivica Lazúrová, CSc., FRCP ²; Ústav lekárskej biochémie Jesseniovej lekárskej fakulty UK Martin, Slovenská republika, vedúci prof. MU Dr. Dušan Dobrota, CSc. ³; Národné referenčné centrum pre dioxíny a príbuzné zlúčeniny Lekárskej fakulty SZU Bratislava, Slovenská republika, vedúci centra Ing. Kamil Čonka ⁴; IV. interná klinika Lekárskej fakulty UPJŠ a UN L. Pasteura Košice, Slovenská republika, prednosta prof. MU Dr. Ivan Tkáč, PhD. ⁵
Published in: Vnitř Lék 2013; 59(5): 352-356
Category: Original Contributions

Overview

Objective:
To find out whether the serum PCB level depends on genetic polymorphism in the area of GSTs genes.

Material and methods:
In the group of 147 men (112 with an average age of 59.1 ± 10.1 and serum PCB level > 1,000 ng/ g lipid – PCB1, and 35 with an average age of 56.2 ± 12.9 and serum PCB level < 700 ng/ g lipid – PCB2), the PCR‑ RLFP analysis of DNA was used to determine the genetic polymorphism in the area of GSTs genes.

Results:
As regards PCB, an association was found between serum PCB concentrations and the null genotype of GSTT1 gene. Men above the median PCB levels displayed, with significantly greater frequency, the null genotype GSTT1 compared to men below the median PCB levels, both in the PCB1 set and in the PCB2 set. In the PCB1 set, the presence of the null genotype GSTT1 increased the risk of high PCB levels 11– fold, in the PCB2 set 4– fold (p < 0.001). In the PCB2 set, an association was also discovered between GSTP1 Val/ Val genotype and higher PCB levels. The risk of high PCB levels in the individuals with the Val/ Val genotype was 5– fold higher than in the carriers of the Ile allele (p < 0.001). In neither set was the GSTM1 genotype associated with serum PCB concentrations.

Conclusion:
The association between high PCB levels and the GSTT1 null and GSTP1 Val/ Val suggests that harmful effects depend not only on the intake amounts of PCB but also on the ability of the organism to detoxify these substances. Individuals living in the same environment are therefore at different risks of developing a disease when exposed to PCB. Polymorphism in the area of GSTTl gene (GSTT1 null) could be a potential genetic risk marker.

Key words:
polychlorinated biphenyls – genetic polymorphism of GSTs genes

Sources

1. Johnson BL, Hicks EH, Jones ED et al. Public Health Implications of Toxic Substances in the Great Lakes and St.Lawrence Basins. J Great Lakes Res 1998; 24: 698– 722.

2. Moreles NM, Tuey DB, Colbrun WA et al. Pharmacokineties of multiple oral doses of selected polychlorinated biphenyls in mice. Toxicol Appl Pharmacol 1997; 48: 397– 470.

3. Kočan A, Petrík J, Drobná B et al. Levels of PCBs and some organochlorine pesticides in the human population of selected areas of the Slovak Republik I. Blood. Chemosphere 1994; 29: 2315– 2325.

4. Jursa S, Chovancová J, Petrík J et al. Dioxin‑like and non‑ dioxin‑like PCBs in human serum of Slovak population. Chemosphere 2006; 64: 689– 691.

5. Petrík J, Drobná B, Pavúk M et al. Serum PCBs and organochlorine pesticides in Slovakia: age, gender, and residence as determinants of organochlorine concentrations. Chemosphere 2006; 65: 408– 410.

6. McKinney JD, Darden T, Lyerly AM et al. PCB and Related Coumpound Binding to the Ah Receptor(s) Theoretical Model Based on Molecular Parameters and Molecular Mechanics. QSAR 2002; 4: 166– 170.

7. Safe SH. Endocrine disruptors and human healt‑ is there a problem. Toxicology 2004; 205: 3– 10.

8. LaRocca C, Mantovani A. From environment to food: the case PCB. Ann Ist Super Sanita 2006; 42: 410– 416.

9. Zmetáková Z, Šalgovičová D. Polychlorované bifenyly, životné prostredie a človek. TRENDY v potravinárstve 2006; 13.

10. Šalgovičová D. Estimation of long‑ term dietary exposure of the inhabitants of Slovac Republic to polychlorinated biphenyls. J Food Nutr Res 2007; 46: 186– 194.

11. Schell ML, Hubicki LA, Gallo MV et al. Organochlorines, lead and mercury in akwesasne Mohawk youth. Environ Health Perspect 2003; 111: 954– 961.

12. James RC, Busch H, Tamburro GH et al. Polychlorynated Biphenyls Exposure and Human Disease. J Occul Environ Med 1993; 35: 136– 148.

13. Colborn T, Vom Saal FS, Soto AM et al. Developmental effects of endocrine‑ disrupting chemicals in wildlife and humans. Environ Health Perspect 1993; 101: 378– 384.

14. Langer P, Tajtáková M, Kočan A et al. Thyroid ultrasound volume, structure and functions after longe term high exposure of large population to polychlorinated biphenyls, pesticides and dioxin. Chemosphere 2007; 69: 118– 127.

15. Hatcher‑ Martin JH, Gearing M, Steenland K et al. Association between polychlorinated biphenyl and Parkinsons Disease neuropathology. Neurotoxicology 2012; 33: 1298– 1304.

16. Šalagovič J, Kalina I, Dudáš M. Genetic polymorphism in xenobiotics metabolizing enzymes as a susceptibility factor to cancer. Bratisl Lek Listy 2000; 101: 512– 521.

17. Zhang Y, Wise JP, Holford TR et al. Serum Polychlorinated Biphenyls, Cytochrome P.450 1A1 Polymorphysms, and Risk of Breast Cancer in Connecticut Wonen. Am J Epidemiol 2004; 160: 1177– 1183.

18. Božina N, Bradamante V, Lovrič M. Genetic Polymorphysm of Metabolic Enzymes P450(CYP) as a Susceptibility Factor for Drug Response. Toxicity and Cancer Risk. Arch Hig Rada Toksikol 2009; 60: 217– 242.

19. Mitra PS, Ghosh S, Zang S et al. Analysis of the toxicogenomic effects of exposure to persistent arganic pollutnts (POPs) in Slovakian girls: correlation between gene expression and disease risk. Environ Int 2012; 39: 188– 199.

20. Brevini AL, Zanetto SB, Cillo F. Effect of endocrine disruptors on developmental and reproductive functions. Current Drug Targets‑ Imnune, Endocrine and Metabolic Disorders 2005; 5: 1– 10.

21. Hrycay EG, Bandiera SM. Spectral interactions of tetrachlorbiphenyls with hepatic microsomal cytochrome P450 enzymes. Chemico‑ Biological Interactions 2003; 146: 285– 296.

22. Mclean MR, Twarowski TP, Robertson LW. Redox cycling of 2- (x’- mono, - di, - trichlorphenyl)-1,4- benzoquinones, oxidation products of polychlorinated biphenyls. Arch Biochem Biophys 2000; 376: 449– 455.

23. Tiwawech D, Chindavijak S, Sornprom A et al. Detection of GSTT1 Polymorphysm in Cancer Patients by Real‑ Time PCR. Thai Cancer J 2008; 28: 172– 183.

24. Dutta SK, Mitra PS, Ghosh S et al. Differential gene expression and functional analysis of PCB‑ exposed children: understanding disease and disorder development. Environ Int 2012; 40: 143– 154.

25. Tamer L, Calikoglu M, Ates NA et al. Glutathion‑ S transferase gene polymorphism (GSTT1,GSTM1,GSTP1) as increased risk factor for asthma. Respirology 2004; 9: 493– 498.

26. Pei Chien Tsai, Wenya Huang, Yeu‑ Chin Lee et al. Genetic Polymorphism in Cyo 1A1 and GSTM1 predispose hunabs to PCBs/ PCSFs‑induced skin lesions. Chemosphere 2006; 63: 1410– 1418.

27. Rybicki BA, Neslund‑ Dudas C, Nock NL et al. Prostate cancer risk from occupational exposure to polycyclic aromatic hydrocarbons interacting with the GSTP1 Ile 105 Val polymorphism. Cancer Detect Prev 2006; 30: 412– 422.

28. Jourenkova‑ Mironova N, Voho A, Bouchardy C et al. Glutathione S‑ transferase GSTM1,GSTM3,GSRP1 and GSTT1 genotypes and the risk of smoking‑ releted oral and pharyngeal cancers. Int J Cancer 1999; 81: 44– 48.

29. Rajagopal R, Deakin M, Fawole AS et al. Glutathion S‑ transferase Tl polymorphisms are associated with outcome in colorectal cancer. Carcinogenesis 2005; 26: 2157– 2163.

30. Economopoulous KP, Sergentamis TN. GSTM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: a comprehensive meta‑analysis. Eur J Cancer 2012; 46: 1617– 1613.

31. Vichi S, Medda E, Ingelido AM et al. Glutathione transferase polymorphisms and risk of endometriosis associated with polychlorinated biphenyls exposure in Italian women: a gene‑ environment interaction. Fertil Steril 2012; 97: 1143– 1151.