• Clinical and Experimental Reproductive Medicine
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• v.31 no.2
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• pp.141-147
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• 2004

Objective: To investigate the association between endometriosis and polymorphisms of N-acetyl transferase 2 (NAT2), glutathione S-transferase M1 (GSTM1), and cytochrome P450 (CYP) 1A1 genes in Korean infertile patients. Materials and Methods: A total of 303 infertile patients who had undertaken diagnostic laparoscopy during January, 2001 through December, 2003 at Samsung Cheil Hospital enrolled in this study. The patients were grouped according to laparoscopic findings: minimal to mild endometriosis (group I: n=147), moderate to severe endometriosis (group II: n=57), normal pelvic cavity (n=99). Peripheral blood was obtained and genomic DNA was extracted. The genotypes of each genes were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). For NAT2, RFLP was used to detect the wild type (wt) and mutant (mt) alleles, enabling classification into slow (mt/mt) or fast (wt/wt or wt/mt) acetylation genotypes. For GSTM1, PCR was used to distinguish active (+/- or +/+) from null (-/-) genotypes. For CYP1A1, MspI digestion was used to detect the wild type (A1A1), heterozygote (A1A2) or mutant (A2A2) genotypes. Result: The genotype frequencies of NAT2 slow acetylator was 12.8%, 10.9%, 12.8% in group I, group II and control, respectively. The genotype frequencies of GSTM1 null mutation was 55.3%, 41.8%, 53.2% in group I, group II and control, respectively. The genotype frequencies of CYP1A1 MspI polymorphism was 16.3%, 9.1%, 18.1% in group I, group II and control, respectively. No significant difference was observed between endometriosis and normal controls in the genotype frequencies of the NAT2, GSTM1, CYP1A1 MspI polymorphism. Conclusion: The NAT2, GSTM1, CYP1A1 gene polymorphism may not be associated with the susceptibility of endometriosis in Korean women.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8815-8822
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• 2014

Background: The incidence of stomach cancer in India is highest in the state of Mizoram. In this population based matched case-control study, we evaluated the relationship between CYP450 2E1 RsaI polymorphism and risk of stomach cancer taking into considering various important dietary habits along with tobacco, alcohol consumption and H. pylori infection status. Materials and Methods: A total of 105 histologically confirmed stomach cancer cases and 210 matched healthy population controls were recruited. CYP2E1 RsaI genotypes were determined by PCR-RFLP and H. pylori infection status by ELISA. Information on various dietary, tobacco and alcohol habits was recorded in a standard questionnaire. Results: Our study revealed no significant association between the CYP2E1 RsaI polymorphism and overall risk of stomach cancer in Mizoram. However, we observed a non-significant protective effect of the variant allele (A) of CYP2E1 against stomach cancer. Tobacco smokers carrying C/C genotype have three times more risk of stomach cancer, as compared to non-smokers carrying C/C genotype. Both Meiziol and cigarette current and past smokers who smoked for more than 10 times per day and carrying the (C/C) genotype are more prone to develop stomach cancer. Smoke dried fish and preserved meat (smoked/sun dried) consumers carrying C/C genotype possesses higher risk of stomach cancer. No significant association between H. pylori infection and CYP2E1 RsaI polymorphism in terms of stomach cancer was observed. Conclusions: Although no direct association between the CYP2E1 RsaI polymorphism and stomach cancer was observed, relations with different tobacco and dietary risk habits in terms of developing stomach cancer exist in this high risk population of north-eastern part of India. Further in-depth study recruiting larger population is required to shed more light on this important problem.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.35 no.2
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• pp.185-190
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• 2002

This study was carried out to measure the in vitro interaction of trialkyltin with the microsomal monooxygenase (MFO) system of the clam, Coelomactra antiquata. Cytochrome P450 (CYP) level and 7-ethonvesorufin-O-deethylase (EROD) activity were invetigated in the microsome isolated from digestive gland of the clam (C. antiquata) exposed to tributyltin chloride (TBTC), bis-tributyltinoxide (TBTO) and triphenyltin chloride (TPTC). The specific contents of CYP in clam microsome exposedto 0.4 mM TBTC, TBTO and TPTC for 20 minutes were decreased 52, 72 and $40\%$, respectively, compared to control group. The EROD activities also were inhibited by exposure to TBTO ($92\%$) and TPTC ($85\%$) except for TBTC, The level of CYP and the EROD actintles were decreased according to the OTC exposure concentrations. The toxic effects on the level of CYP and the EROD activities were in order of TPTC>TBTC>TBTO in this study. The measurement of CYP level and EROD activity could be applied as a biomarker for environmental study.

• Journal of Microbiology and Biotechnology
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• v.13 no.4
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• pp.624-627
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• 2003

Benzo[a]pyrene (B[a]P) is an environmental pollutant that has been implicated in carcinogenesis. Saccharomyces cerevisiae was treated with B[a]P, and the responses of its cytochrome P450 (CYP) enzyme and DNA-damage checkpoint genes were examined through gene expression profiles using a reverse transcription polymerase chain reaction (RT-PCR). The DNA-damage checkpoint genes tested were the chk1 and pds1 genes, involved in a metaphase arrest, the swi6 gene targeted by G1 arrest, the pol2 gene related to S phase arrest, and the cln2 gene encoding a cyclin protein, all of which are based on rad9 and rad24. Among these genes, no noticeable effect was found when the cells were exposed to various concentrations of B[a]P. However, the transcriptional activity of CYP51 was significantly different when the cells were exposed to B[a]P. Accordingly, the present results indicate that cytochrome P450 plays a more significant role than DNA-damage checkpoint genes in the response of S. cerevisiae to B[a]P.

• Biomolecules & Therapeutics
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• v.6 no.3
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• pp.247-255
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• 1998

Carbon tetrachloride (CCI$_4$) induces the hepatotoxicity due to the reactive free radicals generated by cytochrome P-450 (CYP-450) enzyme, which result in destabilization of cellular membrane. Diltiazem, a calcium channel blocking agent, has been known to suppress the CYP-450 enzyme activities. To study the effect of diltiazem in $CCl_4$-treated rats, we measured the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutathione S-transferase (GST), contents of bilirubin, albumin, total protein, cholesterol, triglyceride, blood urea nitrogen, creatinine malondialdehyde and calcium. Also we conducted liver histopathologic examinations. Diltiazem, when administered 1 hour prior to CCI$_4$ treaeent, significantly reduced the activities of ALT and AST, the contents of microsomal malondialdehyde and calcium in liver and microsome as compared with those of $CCl_4$-treated rats. In addition, histopathologic examination showed that diltiazem prevented the development of centrilobular necrosis induced by CCI$_4$ in liver tissue. Our results suggested that diltiazem could inhibit the formation of free radicals and the influx of calcium. Therefore diltiazem may be applied to suppress the liver damage caused by $CCl_4$.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.1
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• pp.82-88
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• 2008

We evaluated the potential protective activity of the traditional Korean medicinal herb, Corni fructus (CF), in an experimental model of hepatotoxicity induced by carbontetrachloride $(CCl_4)$. The CF exhibited a hepatoprotective activity against Chang cell. And The expression of cytochrome P450 2E1 (CYP2E1), measured by RT-PCR and western blot, was significantly decreased in the CF treated Chang cell. But $CCl_4$ and CF has no significant effect on 1A1 and 3A1 isoform of cytochrome P450. Based on these findings, it is suggested that hepatoprotective effects of CF possibly related to antioxidative effects and downregulation of CYP2E1 expression.

• Journal of Life Science
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• v.20 no.5
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• pp.799-804
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• 2010

In humans, CYP2C19, a member of the cytochrome P450 subfamily, metabolizes arachidonic acid to produce epoxyicosanoid acids, which are involved in vascular tone and regulation of blood pressure (BP). Recent findings suggest that CYP2C19 gene polymorphisms might be considered as a novel candidate gene for cardiovascular disease. We thus focused on the Korean population to explore the association of two polymorphisms ($CYP2C19^*2$ and $^*3$) in this gene and essential hypertension (EH). A total of 1,241 participants (537 hypertensive subjects and 704 healthy controls) were recruited from the Yonsei Cardiovascular Genome Center in Korea. The CYP2C19 polymorphisms were genotyped using the $SNaPShot^{TM}$ assay. The allele and genotype frequencies of $CYP2C19^*3$ showed significant difference between hypertensives and normotensives (P=0.019 and P=0.023, respectively). Logistic regression analysis indicated that the $CYP2C19^*3$ A allele carriers were significantly associated with EH (OR, 0.723; 95% CI, 0.538-0.972, P=0.032) under a dominant model. In addition, CYP2C19 G-A haplotype ($2C19^*2\;G-^*3$ A combination) was found to significantly reduce EH risk (OR, 0.714, P=0.015). We believe this provides evidence that $CYP2C19^*3$ polymorphism may contribute to a protective effect in the development of EH.

• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.208-219
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• 2001

The pharmacotherapy of schizophrenia exhibits wide inter-individual variabilities in clinical efficacy and adverse effects. Recently, human genetic diversity has been known as one of the essential factors to the variation in human drug response. This suggests that drug therapy should be tailored to the genetic characteristics of the individual. Pharmacogenetics is the field of investigation that attempts to elucidate genetic basis of an individual's responses to pharmacotherapy, considering drug effects divided into two categories as pharmacokinetics and pharmacodynamics. The emerging field of pharmacogenomics, which focuses on genetic determinants of drug response at the level of the entire human genome, is important for development and prescription of safer and more effective individually tailored drugs and will aid in understanding how genetics influence drug response. In schizophrenia, pharmacogenetic studies have shown the role of genetic variants of the cytochrome P450 enzymes such as CYP2D6, CYP2C19, and CYP2A1 in the metabolism of antipsychotic drugs. At the level of drug targets, variants of the dopamine $D_2$, $D_3$ and $D_4$, and 5-$HT_{2A}$ and 5-$HT_{2C}$ receptors have been examined. The pharmacogenetic studies in schizophrenia presently shows controversial findings which may be related to the multiple involvement of genes with relatively small effects and to the lack of standardized phenotypes. For further development in the pharmacogenomics of schizophrenia, there would be required the extensive outcome measures and definitions, and the powerful new tools of genomics, proteomics and so on.

• Journal of Society of Preventive Korean Medicine
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• v.12 no.3
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• pp.99-113
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• 2008

In this study, the author experimented the influence of five herbal medicines, which are Lonicera japonica Thunb, Paeonia suffruticosa Andr., Fraxinus rhynchophylla Hance, Gardenia jasminoides Ellis, Scutellaria baicalensis George which are called 'Chungyulyak(淸熱藥)' on drug metabolizing enzyme cytochrome P450 3A4 in Human Liver Microsome. Above all, the reason for this study is that herbal medicines can be assumed that herbs might have interactions with drugs, other herbs, alcohol and chemicals whether those are much better synergy effects than expected effects when the medicine was treated alone or not. As a result, we showed that all of five traditional herbal medicines had no CYP 3A4 inhibition effect on 10, 20, 30, 40, $50{\mu}g/m{\ell}$ doses in Human Liver Microsome. However, this result are mostly not enough to prove that PMT has a CYP 3A4 inhibition effect. Moreover, it is not that those rates showed that those herbal medicines have CYP 3A4 induction effect. In conclusion, the result could support that those herbal medicines are more safe than chemical drugs even if this is the basic step to prove that result. Therefore, more specific studies to support this result, which are Kinetic study, cell and animal study then finally until clinical research, are required.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.149-149
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• 2001

Cytochrome P450 (CYP) 2D6 and CYP3A4 have been reported to be involved in the major metabolic pathways and formations of neurotoxic metabolites (HPP$\^$+/, RHPP$\^$+/) from haloperidol (HAL). However, no in vivo study has been addressed to the involvement of both CYP isoforms on the formation of toxic HAL metabolites.(omitted)