Polymorphisms of xenobiotic biotransformation genes and their role in individualization of pharmacological therapy and support of humans after heavy psychophysical loading

Abstract

We analyzed the frequency distribution of CYP1A1, EPHX1, GSTM1, GSTP1, GSTT1 genes polymorphisms in 111 persons exposed to high physical and mental stress (elite athletes). Qualifications of sportsmen ranged from candidates for master of sports to world-class athlete. Comparative analysis revealed significant differences between the main group and the comparison group in the frequency of GSTM1, GSTT1, CYP1A1 genotypes, and a tendency to a predominance of genotype GSTP1 Val / Val in the main group.

Keywords

sport genetics / pharmacogenetics / xenobiotic and drug metabolism / genetic marker / single nucleotide polymorphism

References

[1] Akhmetov I. I. Molecular genetics of sport. Moscow: Soviet Sport, 2009: 126-8, 144-6.

[2] Anzenbacher P., Anzenbacherov E. Cytochromes P450 and metabolism of xenobiotics. Cell Mol Life Sci. 2001; 58 (5-6): 737-7.

[3] Arnold C., Konkel A., Fischer R. et al. Cytochrome P450-dependent metabolism of omega-6 and omega-3 long-chain polyunsaturated fatty acids. Pharmacol. Rep. 2010; 62 (3): 536-47.

[4] Gilliland F. D., Li Y.-F., Saxon A. et al. Effect of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement of allergic responses: randomised, placebo-controlled crossover study. Lancet. 2004; 363: 119-25.

[5] Hung R. J., Boffetta P., Brockmцller J. et al. CYP1A1 and GSTM1 genetic polymorphisms and lung cancer risk in Caucasian non-smokers: a pooled analysis. Carcinogenesis. 2003; 24 (5): 875-82.

[6] Johanson H., Hyland V., Wicking C. et al. DNA elution from buccal cells stored on Whatman FTA Classic Cards using a modified methanol fixation method. Botechniques. 2009; 46 (4): 309-11.

[7] Kalliokoski A., Niemi M. Impact of OATP transporters on pharmacokinetics. Brit. J. Pharmacol. 2009; 158: 693-705.

[8] Laborde E. Glutathione transferases as mediators of signaling pathways involved in cell proliferation and cell death. Cell Death Differ. 2010; 17 (9): 1373-80.

[9] Masetti S., Botto N., Manfredi S. et al. Interactive effect of the glutathione S-transferase genes and cigarette smoking on occurrence and severity of coronary artery risk. J. Mol. Med. 2003; 81 (8): 488-94.

[10] Palmer C. N., Doney A. S., Lee S. P. et al. Glutathione S-transferase M1 and P1 genotype, passive smoking, and peak expiratory flow in asthma. Pediatrics. 2006; 118 (2): 710-6.

[11] Pavanello S., Clonfero E. Biological indicators of genotoxic risk and metabolic polymorphisms. Mutat. Res. 2000; 463: 285-308.

[12] Phillips K. A., Veenstra D. L., Oren E. et al. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA. 2001; 286 (18): 2270-9.

[13] Rotunno M., Yu K., Lubin J. H. et al. Phase I metabolic genes and risk of lung cancer: multiple polymorphisms and mRNA expression. PLoS One. 2009; 4 (5): e5652.

[14] Sarmanov J., Benesov K., Gut I. et al. Genetic polymorphisms of biotransformation enzymes in patients with Hodgkin's and non-Hodgkin's lymphomas. Hum. Mol. Genet. 2001; 10 (12): 1265-73.

[15] Shin A., Kang D., Choi J. Y. et al. Cytochrome P450 1A1 (CYP1A1) polymorphisms and breast cancer risk in Korean women. Exp. Mol. Med. 2007; 39 (3): 361-6.

[16] Siraj A. K., Ibrahim M., Al-Rasheed M. et al. Polymorphisms of selected xenobiotic genes contribute to the development of papillary thyroid cancer susceptibility in Middle Eastern population. BMC Med. Genet. 2008; 5: 9-61.

[17] Wang X., Zuckerman B., Pearson C. et al. Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. JAMA. 2002; 287: 195-202.

[18] Wright C. M., Larsen J. E., Colosimo M. L. et al. Genetic association study of CYP1A1 polymorphisms identifies risk haplotypes in nonsmall cell lung cancer. Eur. Respir. J. 2010; 35 (1): 152-9.

RIGHTS & PERMISSIONS

Kozlova A.S., Pyatibrat A.O., Melnov S.B., Smolnik N.S., Shabanov P.D.