• Title, Summary, Keyword: CYP 450 2E1 RsaI polymorphism

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Functional RsaI/PstI Polymorphism in Cytochrome P450 2E1 Contributes to Bladder Cancer Susceptibility: Evidence from a Meta-analysis

  • Deng, Xiao-Dong;Gao, Qin;Zhang, Bo;Zhang, Li-Xia;Zhang, Wei;Er, Zhe-Er Mu;Xie, Ying;Ma, Ying;Liu, Yun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4977-4982
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    • 2014
  • Background: Cytochrome P450 2E1 (CYP2E1) might be involved in the development of bladder cancer. However, previous studies of any association between CYP2E1 RsaI/PstI polymorphism and bladder cancer risk have yielded conflicting results. In this study, we performed a more precise estimation of the relationship by a meta-analysis based on the currently available evidence from the literature. Method: To assess the effect of CYP2E1 RsaI/PstI polymorphism on bladder cancer susceptibility, a meta-analysis of 6 available studies with 1,510 cases and 1,560 controls were performed through Feb 2014. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the strength of association for CYP2E1 RsaI/PstI polymorphism under different genetic models. Results: When available studies were pooled into the meta-analysis, we found that the C1C2 and C2C2 genotypes of CYP2E1 RsaI/PstI polymorphism significantly decreased bladder cancer risk under different genetic models (heterozygote: OR=0.766, 95%CI=0.613-0.957, $P_{OR}$=0.019; homozygote: OR=0.51, 95%CI=0.303-0.858, $P_{OR}$=0.011; dominant: OR=0.733, 95%CI=0.593-0.905, $P_{OR}$=0.004; recessive: OR=0.565, 95%CI=0.337-0.947, $P_{OR}$=0.030). Subgroup analysis indicated that C2C2 genotype was significantly associated with decreased bladder cancer risk under the homozygote genetic model in Caucasians. There was no evidence of heterogeneity or publication bias. Conclusions: The current meta-analysis suggested that the CYP2E1 RsaI/PstI polymorphism might be associated with bladder cancer susceptibility, especially in Caucasians. Further studies are needed to validate the above conclusion.

Polymorphisms of Cytochrome P450 2E1 Gene in Korean Patients with Renal Failure

  • Yoo, Min
    • Biomedical Science Letters
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    • v.19 no.4
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    • pp.310-314
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    • 2013
  • CYP2E1 in the liver has been studied intensively because it is involved in the metabolic activation of xenobiotics. It is inducible by alcohol, so it has been suspected as the cause of cancer in the stomach and lung. The possible role of CYP2E1 has been suggested strongly as causing tissue damage in mice with renal failure. It was also suspected that 5'-flanking region of CYP2E1 gene might be involved with renal failure. So, we investigated polymorphism of restriction enzyme sites within CYP2E1 gene using the PCR-RFLP analysis. PstI and RsaI sites were located at 5'-flanking region and DraI site was located at intron 6. All three types (W/W, W/S, S/S) were observed for these enzymes although each incidence was somewhat different depending the enzyme sites. W/W was prominent for PstI whereas W/S was markedly high for RsaI. Overall, polymorphic incidence in patients was somewhat higher than normal population. This research should facilitate further investigation of CYP2E1 at genetic level as the direct cause of tissue damage in various organs.

CYP2E1 Genetic Polymorphism with Dietary, Tobacco, Alcohol Habits, H. pylori Infection Status and Susceptibility to Stomach Cancer in Mizoram, India

  • Malakar, Mridul;Devi, K. Rekha;Phukan, Rup Kumar;Kaur, Tanvir;Deka, Manab;Puia, Lalhriat;Baruah, Debajit;Mahanta, Jagadish;Narain, Kanwar
    • 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.

Single Nucleotide Polymorphism in Cytochrome P450 2E1 among Korean Patients on Warfarin Therapy

  • Han, Dong-Hoon;Lee, Min-Jeon;Kim, Jeong-Hee;Lee, Suk-Hyang
    • Biomolecules & Therapeutics
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    • v.14 no.4
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    • pp.189-193
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    • 2006
  • This study was designed to assess the distribution of cytochrome P450 2E1 (CYP2E1) polymorphism among Korean patients on warfarin therapy. CYP2E1 polymorphism was analyzed at 5' flanking region of CYP2E1 gene using restriction fragment length polymorphism method. Patient characteristics including the measured internal normalized ratio (INR) were also evaluated. Based on the warfarin dose and the bleeding cases, the patients were grouped as the regular dose control, the regular dose bleeding, the low dose control, and the low dose bleeding. Total 96 patients were evaluated for both Pst I and Rsa I loci of the CYP2E1 gene and the results showed that both loci were tightly linked. Thirty-three patients(34.4%) were heterozygotes and 4 patients(4.2%) were homozygote. There was no significant difference in patient characteristics in the dose and bleeding case groups. CYP2E1 polymorphism showed a little difference among the groups but was not statistically significant, however, lower INR value was observed in homozygote genotype groups. It was also revealed that genotype allele frequencies of CYP2E1 in Korean was close to other Asian groups but was significantly different from other Caucasian and African-American populations.

Action-mechanisms of Genetic Polymorphism in the CYP2E1 on Susceptibility to Polycyclic Aromatic Hydrocarbons (다환성방향족탄화수소 노출에 대한 감수성에 미치는 CYP2E1의 작용)

  • Kang Hyuck-Joon;Park Chang- Hwan;Kang Jin Sun;Dong Mi- Sook;Yang Mihi
    • Environmental health and toxicology
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    • v.20 no.3
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    • pp.215-221
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    • 2005
  • Environmental polycyclic aromatic hydrocarbones (PAHs), which are formed during incomplete combustion of fossil fuels, are widely distributed in our environment. Human exposure to PAHs may occur through smoking, polluted air, food consumption and occupational contact. Urinary naphthols, 1-and 2-naphthol, have been suggested as route -specific biomarkers for exposure to airborne PAHs. Cytochrome p450 2E1 (CYP2E1) is known to be a great importance for the metabolism of organic solvents, which is a precacinogens with small molecular weight. This study describes the metabolic differences between PstI and RsaI polymorphisms (c1 allele: PstI-. RsaI+ ; c2 allele: PstI+, RsaI-) of CYP2E1 5-flanking region by genetically modified HepG2 cells, which overexpress the polymorphic regions. The results of CAT assay and western blot in the c2 allele overexpressed cells have higher activities than the cl allele over-expressing cells. However, the metabolism of naphthalene to 2-naphthol has no difference due to the two genotypes. In this study, we established the CYP2E1 polymorphic allele transduced HepG2 cells to screen susceptibility -differences in PAH exposure. In conclusion, the CYP2E1 polymorphism may hardly induce susceptibility differences in PAH exposure monitoring with urinary naphthols.

Roles of CYP1A1 and CYP2E1 Gene Polymorphisms in Oral Submucous Fibrosis

  • Yaming, Punyo;Urs, Aadithya Basavaraj;Saxena, Alpana;Zuberi, Mariyam
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3335-3340
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    • 2016
  • Background: Oral submucous fibrosis (OSF) is a precancerous condition with a 4 to13% malignant transformation rate. Related to the habit of areca nut chewing it is mainly prevalent in South-east Asian countries where the habit of betel quid chewing is frequently practised. On chewing, alkaloids and polyphenols are released which undergo nitrosation and give rise to N-nitrosamines which are cytotoxic agents. CYP450 is a microsomal enzyme group which metabolizes various endogenous and exogenous chemicals including those released by areca nut chewing. CYP1A1 plays a central role in metabolic activation of these xenobiotics, whereas CYP2E1 metabolizes nitrosamines and tannins. Polymorphisms in genes that code for these enzymes may alter their expression or function and may therefore affect an individuals susceptibility regarding OSF and oral cancer. The present study was therefore undertaken to investigate the association of polymorphisms in CYP1A1 m2 and CYP2E1 (RsaI/PstI) sites with risk of OSF among areca nut chewers in the Northern India population. A total of 95 histopathologically confirmed cases of OSF with history of areca nut chewing not less than 1 year and 80, age and sex matched controls without any clinical signs and symptoms of OSF with areca nut chewing habit not less than 1 year were enrolled. DNA was extracted from peripheral blood samples and polymorphisms were analyzed by PCR-RFLP method. Gene polymorphism of CYP1A1 at NcoI site was observed to be significantly higher (p = 0.016) in cases of OSF when compared to controls. Association of CYP1A1 gene polymorphism at NcoI site and the risk of OSF (Odd's Ratio = 2.275) was also observed to be significant. However, no such association was observed for the CYP2E1 gene polymorphism (Odd's Ratio = 0.815). Our results suggest that the CYP1A1 gene polymorphism at the NcoI site confers an increased risk for OSF.