Five genetic polymorphisms of cytochrome P450 enzymes in the Czech non-Roma and Czech Roma population samples

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Lucie Dlouhá ◽  
Věra Adámková ◽  
Lenka Šedová ◽  
Věra Olišarová ◽  
Jaroslav A. Hubáček ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Genetic Polymorphisms ◽  
Metabolic Pathways ◽  
Cytochromes P450 ◽  
Taqman Assay ◽  
Cytochrome P450 Enzymes ◽  
Roma Population ◽  
Czech Population ◽  
Genotype Frequencies ◽  
Pcr Rflp

AbstractObjectivesCytochromes P450 play a role in human drugs metabolic pathways and their genes are among the most variable in humans. The aim of this study was to analyze genotype frequencies of five common polymorphisms of cytochromes P450 in Roma/Gypsy and Czech (non-Roma) population samples with Czech origin.MethodsRoma/Gypsy (n=302) and Czech subjects (n=298) were genotyped for CYP1A2 (rs762551), CYP2A6 (rs4105144), CYP2B6 (rs3745274) and CYP2D6 (rs3892097; rs1065852) polymorphisms using PCR-RFLP or Taqman assay.ResultsWe found significant allelic/genotype differences between ethnics in three genes. For rs3745274 polymorphism, there was increased frequency of T allele carriers in Roma in comparison with Czech population (53.1 vs. 43.7%; p=0.02). For rs4105144 (CYP2A6) there was higher frequency of T allele carriers in Roma in comparison with Czech population (68.7 vs. 49.8%; p<0.0001). For rs3892097 (CYP2D6) there was more carriers of the A allele between Roma in comparison with Czech population (39.2 vs. 38.2%; p=0.048). Genotype/allelic frequencies of CYP2D6 (rs1065852) and CYP1A2 (rs762551) variants did not significantly differ between the ethnics.ConclusionsThere were significant differences in allelic/genotype frequencies of some, but not all cytochromes P450 polymorphisms between the Czech Roma/Gypsies and Czech non-Roma subjects.

scholarly journals Association of Genetic Polymorphisms and Serum Levels of IL-6 and IL-8 with the Prognosis in Children with Neuroblastoma

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 529
Author(s):  
Silvia Selene Moreno-Guerrero ◽  
Arturo Ramírez-Pacheco ◽  
Luz María Rocha-Ramírez ◽  
Gabriela Hernández-Pliego ◽  
Pilar Eguía-Aguilar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Genetic Polymorphisms ◽  
Poor Prognosis ◽  
Serum Levels ◽  
Control Group ◽  
Mexican Children ◽  
Genotype Frequencies ◽  
Pcr Rflp ◽  
The Impact ◽  
Circulating Levels

There is evidence that high circulating levels of IL-6 and IL-8 are markers of a poor prognosis in various types of cancer, including NB. The participation of these cytokines in the tumor microenvironment has been described to promote progression and metastasis. Our objective was to evaluate the prognostic role of genetic polymorphisms and serum levels of IL-6 and IL-8 in a cohort of Mexican pediatric patients with NB. The detection of the SNPs rs1800795 IL-6 and rs4073 and rs2227306 IL-8 was carried out by PCR-RFLP and the levels of cytokines were determined by the ELISA method. We found elevated circulating levels of IL-8 and IL-6 in NB patients compared to the control group. The genotype frequencies of the rs1800795 IL-6 and rs4073 IL-8 variants were different between the patients with NB and the control group. Likewise, the survival analysis showed that the GG genotypes of rs1800795 IL-6 (p = 0.014) and AA genotypes of rs4073 IL-8 (p = 0.002), as well as high levels of IL-6 (p = 0.009) and IL-8 (p = 0.046), were associated with lower overall survival. We confirmed the impact on an adverse prognosis in a multivariate model. This study suggests that the SNPs rs1800795 IL-6 and rs4073 IL-8 and their serum levels could be promising biomarkers of a poor prognosis, associated with overall survival, metastasis, and a high risk in Mexican children with NB.

Genetic polymorphisms of cytochrome P450 enzymes influence metabolism of the antidepressant escitalopram and treatment response

2010 ◽  
Vol 11 (4) ◽  
pp. 537-546 ◽  
Author(s):  
Ming-Hsien Tsai ◽  
Keh-Ming Lin ◽  
Mei-Chun Hsiao ◽  
Winston W Shen ◽  
Mong-Liang Lu ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Treatment Response ◽  
Genetic Polymorphisms ◽  
Cytochrome P450 Enzymes

scholarly journals Characterization of O-demethylations and Aromatic Hydroxylations Mediated by Cytochromes P450 in the Metabolism of Flavonoid Aglycons

2019 ◽  
Vol 92 (1) ◽  
pp. 115-123 ◽  
Author(s):  
Goran Benković ◽  
Hrvoje Rimac ◽  
Željan Maleš ◽  
Siniša Tomić ◽  
Zoran Lončar ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Cytochromes P450 ◽  
Liver Microsomes ◽  
Cytochrome P450 Enzymes ◽  
Uv Detector ◽  
Aromatic Hydroxylation ◽  
Metabolism Of Xenobiotics ◽  
Kinetics Of

One of the most important groups of metabolic enzymes is cytochrome P450 superfamily. These enzymes are important in terms of the catalytic diversity and the large number of xenobiotics that are detoxified or activated by converting to reactive metabolites. Flavonoids are xenobiotics to which humans are exposed through diet. Data on their oxidative metabolism mediated by cytochromes P450 are limited. The aim of this study was to determine the enzymatic kinetics of O-demethylation and aromatic hydroxylation of flavonoid aglycons on recombinant cytochrome P450 enzymes and human liver microsomes systems. The study was performed on ten flavonoids, namely 3,7-dihydroxyflavone, 7-hydroxyflavone, acacetin, apigenin, flavone, galangin, kaempferol, naringenin, sakuranetin, and tangeretin using liquid chromatography coupled with mass spectrometry and UV detector. Most relevant enzyme involved in metabolism of flavonoid aglycons is CYP1A2, and its catalytic effectiveness ranges from 0.5 to 2.9 × 106 M–1 min–1. Having in mind high expression and involvement of CYP1A2 in metabolism of xenobiotics including drugs, and its intraindividual differences in expression and activity, potential of drug-flavonoid competitive interactions/inhibitions should be considered when consuming dietary supplement and foods rich in flavonoids.

scholarly journals Effects of Genetic Polymorphisms of Drug Transporter ABCB1 (MDR1) and Cytochrome P450 Enzymes CYP2A6, CYP2B6 on Nicotine Addiction and Smoking Cessation

2020 ◽  
Vol 11 ◽  
Author(s):  
Ahmet Muderrisoglu ◽  
Elif Babaoglu ◽  
Elif Tugce Korkmaz ◽  
Mert C. Ongun ◽  
Erdem Karabulut ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Cytochrome P450 ◽  
Drug Treatment ◽  
Genetic Polymorphisms ◽  
Genetic Variants ◽  
Smoking Status ◽  
Turkish Population ◽  
Drug Transporter ◽  
Cytochrome P450 Enzymes ◽  
Quit Smoking

ObjectivesTo determine the effects of genetic polymorphisms of ABCB1 (MDR1), CYP2A6, CYP2B6 on smoking status, and clinical outcomes of smoking cessation therapies in a Turkish population.Methods130 smokers and 130 non-smokers were recruited. Individuals who never smoked were described as non-smokers. 130 smokers were treated with nicotine replacement therapy (NRT) (n = 40), bupropion (n = 47), bupropion + NRT (n = 15), and varenicline (n = 28). Smokers were checked by phone after 12 weeks of treatment whether they were able to quit smoking or not. Genotyping and phenotyping were performed.ResultsCessation rates were as follows; 20.0% for NRT, 29.8% for bupropion, 40.0% for bupropion + NRT, 57.1% for varenicline (p = 0.013). The frequency of ABCB1 1236TT-2677TT-3435TT haplotype was significantly higher in non-smokers as compared to smokers (21.5% vs. 10.8, respectively; p = 0.018). Neither smoking status nor smoking cessation rates were associated with genetic variants of CYP2A6 (p = 0.652, p = 0.328, respectively), or variants of CYP2B6 (p = 0.514, p = 0.779, respectively).ConclusionGenetic variants of the drug transporter ABCB1 and the 1236TT-2677TT-3435TT haplotype was significantly associated with non-smoking status. Neither ABCB1 nor CYP2A6, CYP2B6 genetic variants were associated with smoking cessation rates at the 12th week of drug treatment.

scholarly journals Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in a healthy Mongolian population in China

2010 ◽  
Vol 9 (3) ◽  
pp. 1844-1851 ◽  
Author(s):  
Z.F. Yang ◽  
H.W. Cui ◽  
T. Hasi ◽  
S.Q. Jia ◽  
M.L. Gong ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Genetic Polymorphisms ◽  
Cytochrome P450 Enzymes

scholarly journals Unrivalled diversity: the many roles and reactions of bacterial cytochromes P450 in secondary metabolism

2018 ◽  
Vol 35 (8) ◽  
pp. 757-791 ◽  
Author(s):  
Anja Greule ◽  
Jeanette E. Stok ◽  
James J. De Voss ◽  
Max J. Cryle
Keyword(s):  
Cytochrome P450 ◽  
Secondary Metabolism ◽  
Cytochromes P450 ◽  
Chemical Transformations ◽  
Cytochrome P450 Enzymes ◽  
The Many

This review highlights the scope of chemical transformations that cytochrome P450 enzymes catalyse within bacterial secondary metabolism.

scholarly journals Genetics of Nevirapine Metabolic Pathways at Steady State in HIV-Infected Cambodians

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Philippine Eloy ◽  
Adrien Tessier ◽  
Patty Fan-Havard ◽  
Monidarin Chou ◽  
Céline Verstuyft ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Steady State ◽  
Genetic Polymorphisms ◽  
Metabolic Pathways ◽  
Hydroxylated Metabolites ◽  
Cyp Isoforms ◽  
Hepatic Cytochrome

ABSTRACT Nevirapine is metabolized by several hepatic cytochrome P450 (CYP) isoforms to generate four primary hydroxylated metabolites: 2-hydroxynevirapine, 3-hydroxynevirapine, 8-hydroxynevirapine, and 12-hydroxynevirapine. The present study characterized associations between genetic polymorphisms and metabolite ratios in HIV-infected Cambodians. We demonstrate associations between CYP2B6 polymorphisms and metabolite ratios for both 3-hydroxynevirapine and 8-hydroxynevirapine, suggesting involvement of CYP2B6 in generating these metabolites.

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