scholarly journals CYP3A4*1G gene Polymorphism on Javanese People

2015 ◽  
Vol 16 (2) ◽  
pp. 83
Author(s):  
Em Sutrisna ◽  
Iwan Dwiprahasto ◽  
Erna Kristin
Keyword(s):  
Cytochrome P450 ◽  
Catalytic Activity ◽  
Gene Polymorphism ◽  
Japanese Population ◽  
Genotype Frequency ◽  
Cytochrome P450 3A4 ◽  
Weinberg Equilibrium ◽  
Hardy Weinberg Equilibrium ◽  
Cyp3a4 Gene ◽  
Cytochrome P 450

Most of drugs are metabolized by cytochrome P 450 (CYP) enzyme. Cytochrome P450 3A4 is thecytochrome that is involved in metabolizing more than 60% of all medicine used in human. The variationof this CYP3A4 gene will affect the catalytic activity of this enzyme. Recently, CYP3A4*1G in intron 10 wasfound in Chinese and Japanese population. There is a substitution of G to A at position 82266 in intron 10. Thepurpose of this research was to investigate the frequency of allele and genotype CYP3A4*1G. Samples weretaken from bloods of the subjects of the research. The examination of CYP3A4*1G was conducted by RTLP-PCRmethod.As the results of this research, the frequency of CYP3A4*1G in Javanese people is CYP3A4*1/*1 0.25,CYP3A4*1/*1G 0.55 and CYP3A4*1G/*1G 0.20. Frequency of allele G: 0.53, allele A: 0.47. The Fisher’s exact- testshows that the allele and genotype frequencyis p. 1.000. The allele and genotype frequency of Javanese peopleisstill in Hardy-Weinberg equilibrium.

scholarly journals Potential Role for Human Cytochrome P450 3A4 in Estradiol Homeostasis

Endocrinology ◽  
2005 ◽  
Vol 146 (7) ◽  
pp. 2911-2919 ◽  
Author(s):  
Ai-Ming Yu ◽  
Katsumi Fukamachi ◽  
Kristopher W. Krausz ◽  
Connie Cheung ◽  
Frank J. Gonzalez
Keyword(s):  
Cytochrome P450 ◽  
Mammary Glands ◽  
Cytochrome P450 3A4 ◽  
Wild Type ◽  
Lactating Mothers ◽  
Human Cytochrome ◽  
Pup Survival ◽  
Cyp3a4 Inhibitors ◽  
Cyp3a4 Gene ◽  
Estradiol Levels

Abstract Previously, a human CYP3A4-transgenic (Tg-CYP3A4) mouse line was reported to exhibit enhanced metabolism of midazolam by cytochrome P450 3A4 (CYP3A4) expressed in small intestine. Here we show that expression of CYP3A4 and murine cyp3a and cyp2b was both age and sex dependent. CYP3A4 was expressed in the livers of male and female Tg-CYP3A4 mice at 2 and 4 wk of age. Since 6 wk, CYP3A4 was undetectable in male livers, whereas it was constitutively expressed in female livers at decreased levels (3- to 5-fold). Pregnenolone 16α-carbonitrile markedly induced hepatic CYP3A4 expression, and the level was higher in females than males. Induction of intrinsic murine cyp3a and cyp2b was also sex dependent. Tg-CYP3A4 females were found to be deficient in lactation, leading to a markedly lower pup survival. The mammary glands of the Tg-CYP3A4 lactating mothers had underdeveloped alveoli with low milk content. Furthermore, β-casein and whey acidic protein mRNAs were expressed at markedly lower levels in Tg-CYP3A4 pregnant and nursing mouse mammary glands compared with wild-type mice. This impaired lactation phenotype was associated with significantly reduced serum estradiol levels in Tg-CYP3A4 mice. A pharmacokinetic study revealed that the clearance of iv administrated [3H]estradiol was markedly enhanced in Tg-CYP3A4 mice compared with wild-type mice. These results suggest that CYP3A4 may play an important role in estradiol homeostasis. This may be of concern for treatment of pregnant and lactating women because CYP3A4 gene expression and enzymatic activity can be potentially modified by CYP3A4 inhibitors or inducers in medications, supplements, beverages, and diet.

Taurine modulates catalytic activity of cytochrome P450 3A4

2015 ◽  
Vol 80 (3) ◽  
pp. 366-373 ◽  
Author(s):  
V. V. Shumyantseva ◽  
A. A. Makhova ◽  
T. V. Bulko ◽  
R. Bernhardt ◽  
A. V. Kuzikov ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Catalytic Activity ◽  
Cytochrome P450 3A4

No effect of lipoic acid on catalytic activity of cytochrome P450 3A4

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Anna A. Makhova ◽  
Evgeniya V. Shikh ◽  
Tatiana V. Bulko ◽  
Andrei A. Gilep ◽  
Sergei A. Usanov ◽  
...  
Keyword(s):  
Experimental Data ◽  
Cytochrome P450 ◽  
Catalytic Activity ◽  
Lipoic Acid ◽  
Negative Impact ◽  
Chelating Agent ◽  
The Body ◽  
Model Systems ◽  
Cytochrome P450 3A4 ◽  
Complex Therapy

AbstractObjectivesα-Lipoic acid is used as an antioxidant in multivitamin formulations to restore the normal level of intracellular glutathione after depletion caused by environmental pollutants or during physiological aging of the body, as a chelating agent, as a dietary supplement, in anti-aging compositions. Lipoic acid (LA) acts as a buffer in cancer therapy and in therapy of diseases associated with oxidative stress. The effect of LA on the catalytic functions of cytochrome P450 3A4 as the main enzyme of the biotransformation of drugs was studied. It was shown that LA in the concentration range of 50–200 μM affects the stage of electron transfer (stage of cytochrome P450 3A4 heme reduction), decreasing the cathodic reduction current by an average of 20 ± 5%. The kinetic parameters (kcat) of the N-demethylation reaction of erythromycin, the antibiotic of the macrolide group, used as a marker substrate for the comparative analysis of the catalytic activity of cytochrome P450 3A4, both in the presence of α-lipoic acid and in the cytochrome P450 3A4-erythromycin complex, amounted to comparable values of 3.5 ± 0.9 and 3.4 ± 0.9 min−1, respectively. Based on these experimental data, we can conclude that there is no significant effect of α-lipoic acid on the catalysis of cytochrome P450 3A4. These results can be projected on the possibility of using α-lipoic acid in complex therapy without negative impact on the enzymatic cytochrome P450 system.MethodsThe analysis was performed in electrochemical non-invasive model systems for recording the catalytic activity of cytochrome P450 3A4, using screen-printed electrodes, modified with membranous didodecyldimethylammonium bromide.ResultsIt was shown that LA did not affect the N-demethylation of macrolide antibiotic erythromycin. Catalytic constant (kcat) of N-demethylation of erythromycin corresponds to 3.4 ± 0.9 min−1 and in the presence of LA corresponds to 3.5 ± 0.9 min−1.ConclusionsBased on the obtained experimental data, we can conclude that there is no significant effect of α-lipoic acid on individual stages and processes of catalysis of cytochrome P450 3A4. LA can be recommended for inclusion in complex therapy as an antioxidant, antitoxic and chelating compound without negative impact on the enzymatic cytochrome P450 3A4 activity of the human body.

Geographic distribution of the 3435C>T polymorphism of the MDR1 gene in Peruvian populations

2019 ◽  
Vol 34 (3) ◽  
Author(s):  
Edward Valencia Ayala ◽  
Pool Marcos Carbajal ◽  
Eduardo Barbosa Coelho ◽  
Jose Sandoval Sandoval ◽  
Alberto Salazar Granara
Keyword(s):  
Genetic Polymorphisms ◽  
Geographic Distribution ◽  
Allele Frequencies ◽  
Genotype Frequency ◽  
Mdr1 Gene ◽  
Frequency Distributions ◽  
Weinberg Equilibrium ◽  
Pearson Test ◽  
Hardy Weinberg Equilibrium ◽  
Genotype And Allele Frequencies

Abstract Background The MDR1 gene presents several genetic polymorphisms with pharmacological implications. Therefore, the aim of the present study is to establish the genotype and allele frequencies of 3435C>T polymorphism of MDR1 gene into Peruvian populations (Coastal, Andean and Amazonian ecoregions), even considering the altitude (lowland <2500 m and highland >2500 m). Methods The polymorphism was analyzed by TaqMan genotyping assays in a group of 181 healthy unrelated Peruvian individuals. The comparison of genotype and allele frequencies of 3435C>T polymorphism was made with the Pearson test (X2), and, to calculate the genotype distributions, the Hardy-Weinberg equilibrium (HWE) was used. Results In all populations evaluated in this study, the genotype frequency distributions met HWE assumptions. The comparison between genotype and allele frequencies showed significant differences (p < 0.05), when the Andean, Coastal and Amazonian populations were compared. Also, significant differences (p < 0.05) were obtained when these populations were compared considering their altitudes. Likewise, in comparison with countries like USA, Finland, Nigeria and Kenya, the results showed significant differences (p < 0.05). Conclusions This investigation allowed us to establish the genotype and allele frequencies of 3435C>T polymorphism in different Peruvian populations, considering the geographic localization and even the altitude.

scholarly journals Association of Klotho Gene Polymorphism with Cerebral Infarction

2021 ◽  
Author(s):  
Yu Li ◽  
Qiang Zhang ◽  
Haiping Bao ◽  
Chen Nie
Keyword(s):  
Gene Polymorphism ◽  
Cerebral Infarction ◽  
Peripheral Blood ◽  
Promoter Region ◽  
Gene Polymorphisms ◽  
Expression Level ◽  
Control Group ◽  
Weinberg Equilibrium ◽  
Klotho Gene ◽  
Hardy Weinberg Equilibrium

Background: We aimed to investigate the expression of Klotho gene in peripheral blood of patients with cerebral infarction (CI) and the association of its polymorphisms with the occurrence of CI. Methods: A total of 60 CI patients (CI group) and 20 healthy people receiving physical examination (control group) were enrolled as the research subjects. The expression of Klotho gene in CI group and control group was determined using enzyme-linked immunosorbent assay kit. Single nucleotide polymorphisms (rs192031, rs200131 and rs102312) in the promoter region of the Klotho gene were typed via conformational difference gel electrophoresis. Besides, whether the distribution frequencies of Klotho genotypes conformed to Hardy-Weinberg equilibrium was evaluated by chi-square test. Meanwhile, the associations of Klotho alleles and gene polymorphisms with CI occurrence were analyzed. Results: The protein expression level of Klotho in the peripheral blood was remarkably lower in patients in CI group than that in control group (P<0.05). Hardy-Weinberg equilibrium analysis revealed that Klotho gene polymorphisms (rs192031, rs200131 and rs102312) conformed to the genetic equilibrium distribution (P>0.05). Gene-based association analysis manifested that only rs192031 polymorphism and alleles were correlated with CI occurrence (P<0.05). Systolic blood pressure and high-density lipoprotein cholesterol were notably higher in CI patients with TT genotype of Klotho gene polymorphism rs192031 than those in control group (P<0.05). Furthermore, there were no associations of rs200131 and rs102312 polymorphisms and alleles with the occurrence of CI (P>0.05). Conclusions: The expression level of Klotho is evidently reduced in the peripheral blood of CI patients. Rs192031 in the promoter region of the Klotho gene is associated with the occurrence of CI, while rs200131 and rs102312 have no relations with CI.

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