Pharmacogenetic relevant polymorphisms of CYP2C9, CYP2C19, CYP2D6, and CYP3A5 in Bhutanese population

Dorji, Palden Wangyel; Wangchuk, Sonam; Boonprasert, Kanyarat; Tarasuk, Mayuri; Na‐Bangchang, Kesara

doi:10.1515/dmpt-2019-0020

Cited by 8 publications

(3 citation statements)

References 44 publications

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“…As is known, VPA is metabolized by three routes including (1) glucuronide conjugation by several uridine glucuronyl transferases (UGTs), (2) mitochondrial β-oxidation, and (3) oxidation by several cytochrome P450 (CYP450) enzymes [36,37]. Interethnic variability in CYP450 and UGT allele frequencies has been reported among Asian, African, and Caucasian populations [38][39][40][41]. Enzyme polymorphisms in VPA metabolic enzymes, including CYP2C9, CYP2C19, UGT1A4, and UGT2B7, may influence VPA concentrations [34,35,[42][43][44][45], and some PPK models have identified the effects of genetic variants on VPA clearance and included metabolic enzyme genotypes as covariates [34,35,42].…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of valproic acid in adult Chinese patients with bipolar disorder

Zang

Guo

Niu

et al. 2021

Eur J Clin Pharmacol

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Purpose To develop and validate a population pharmacokinetic (PPK) model of valproic acid (VPA) in adult Chinese patients with bipolar disorder, and provide guidance for individualized therapy in this population. Methods A total of 1104 serum concentrations from 272 patients were collected in this study. The data analysis was performed using a nonlinear mixed-effects modeling approach. Covariates included demographic parameters, biological characteristics, and concomitant medications. Bootstrap validation (1000 runs), normalized prediction distribution error (NPDE), and external validation of 50 patients were employed to evaluate the final model. ResultsA one-compartment model with first-order absorption and elimination was developed for VPA extended-release tablets. VPA clearance was significantly influenced by three variables: sex (12% higher in male patients), daily dose (increasing with the 0.13 exponent), and body weight (increasing with the 0.56 exponent). Typical values for the absorption rate constant (K a ), apparent clearance (CL/F), and apparent distribution volume (V/F) for a female patient weighing 70 kg administered VPA 1000 mg/day were 0.18 h −1 , 0.46 L/h, and 12.84 L, respectively. The results of model evaluation indicated a good stable and precise performance of the final model. Conclusions A qualified PPK model of VPA was developed in Chinese patients with bipolar disorder. This model could be used as a suitable tool for the personalization of VPA dosing for bipolar patients.

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Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of valproic acid in adult Chinese patients with bipolar disorder

Zang

Guo

Niu

et al. 2021

Eur J Clin Pharmacol

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“…20 The percentages of CYP2C19 EM, IM, and PM phenotypes was 48.22%, 42.98%, and 6.64% in a Thai population, 21 41.20%, 24.07%, and 4.17% in the population of the Republic of Srpska. 22 The prevalence of CYP2C19 EM, IM, and PM phenotypes was 75.97%, 21.91%, and 2.21% in a Greek population. 23 In Moroccan population, the percentages of CYP2C19 EM, IM, and PM phenotypes was 83.45%, 14.14%, and 2.41%, respectively, 24 the percentages was 75.8%, 21.1%, and 3.1% in Lebanese population.…”

Section: Discussionmentioning

confidence: 90%

Differences in the Proportion of CYP2C19 Loss-of-Function Between Cerebral Infarction and Coronary Artery Disease Patients

Shi¹,

Yang²,

Feng³

et al. 2023

IJGM

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Background: Cytochrome P450 2C19 (CYP2C19) genotypes and metabolic phenotypes (extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM)) are related to the metabolism of therapeutic drugs for cardiovascular and cerebrovascular diseases. This study aimed to investigate the differences of CYP2C19 gene polymorphism distribution between coronary artery disease (CAD) patients and cerebral infarction (CI) patients. Methods: We identified 413 CI patients, 509 CAD patients, and 241 CI+CAD patients from 2016 to 2020 and studied genotypes of CYP2C19 rs4986893 (636G>A) and rs4244285 (681G>A) polymorphisms using PCR-gene chip detection method. Differences in CYP2C19 genotypes and metabolic phenotypes between the groups were compared. To analyze the efficacy of CYP2C19 metabolic phenotypes in discriminating between cerebral infarction and coronary artery disease, multiple logistic regression analysis was conducted after adjusting for gender, age, smoking history, drinking history, hypertension, and diabetes. Results: There were significant differences in the distribution of CYP2C19 genotypes and metabolic phenotypes between CI and CAD patients. The results of multivariate logistic regression (adjusted for sex, age, smoking, drinking, hypertension, and diabetes) indicated that CYP2C19 IM phenotype (IM vs EM: OR 1.443, 95% CI: 1.086-1.918, P=0.011) and CYP2C19 IM+PM phenotype (IM or PM vs EM: OR 1.440, 95% CI: 1.100-1.885, P=0.008) may be indicators of CI from CAD. Conclusion: CYP2C19 EM metabolic phenotype was dominant in CAD patients, and CYP2C19 IM metabolic phenotype was dominant in CI patients. After adjusting for other confounding factors, patients with the CYP2C19 IM metabolic phenotype were more likely to develop CI than CAD.

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“…The percentage of CYP2C19*1, *2, and *3 allele was 76%, 20.5%, and 2.5% in the Vietnamese population, respectively [40]. The percentage of CYP2C19*2, and *3 allele was 25.60% and 2.50% in a Thai population [41], 30.14% and 15.69% in Bhutanese population [42]. The prevalence of the CYP2C19*2 allele was 16.3% in the population from the Republic of Srpska in Bosnia and Herzegovina [43], and 13.1% in a Greek population [44].…”

Section: Discussionmentioning

confidence: 92%

CYP2C19 loss-of-function is associated with increased risk of hypertension in a Hakka population: a case-control study

Cai

et al. 2023

BMC Cardiovasc Disord

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Background Genetic factors have a certain proportion in the risk factors of hypertension. The purpose was to investigate the relationship of cytochrome P450 2C19 (CYP2C19) polymorphisms with hypertension in Hakka population. Methods The study included 1,872 hypertensive patients and 1,110 controls. The genotypes of CYP2C19 rs4244285 and rs4986893 of all individuals were detected and analyzed. Results The genotype and allele distributions of CYP2C19 rs4244285 were significantly different between hypertension group and control group. The CYP2C19 *1/*1 genotype was the most predominant among the subjects (40.8%), followed by the CYP2C19 *1/*2 genotype (40.5%). The percentage of CYP2C19*1, *2, and *3 allele was 64.2%, 30.8%, and 5.0%, respectively. The proportion of intermediate metabolizers (IM) (49.3% vs. 42.9%), poor metabolizers (PM) (14.3% vs. 8.9%) (P < 0.001), and CYP2C19*2 allele (33.8% vs. 25.7%, P < 0.001) in hypertension group was significantly higher than that in control group. Multivariate logistic regression (adjusted for gender, age, smoking, and drinking) indicated that CYP2C19 *1/*2, *1/*3, and *2/*2 genotypes may increase susceptibility to hypertension. And the CYP2C19 IM genotype (IM vs. EM: OR 1.514, 95% CI: 1.291–1.775, P < 0.001), PM genotype (PM vs. EM: OR 2.120, 95% CI: 1.638–2.743, P < 0.001), IM + PM genotypes (IM + PM vs. EM: OR 1.617, 95% CI: 1.390–1.882, P < 0.001) may increase risk of hypertension. Conclusions CYP2C19 loss-of-function (IM, PM genotypes) is independent risk factor for hypertension susceptibility. Specifically, the risk genotypes include CYP2C19 *1/*2, *1/*3, and *2/*2.

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Pharmacogenetic relevant polymorphisms of CYP2C9, CYP2C19, CYP2D6, and CYP3A5 in Bhutanese population

Cited by 8 publications

References 44 publications

Population pharmacokinetics of valproic acid in adult Chinese patients with bipolar disorder

Population pharmacokinetics of valproic acid in adult Chinese patients with bipolar disorder

Differences in the Proportion of CYP2C19 Loss-of-Function Between Cerebral Infarction and Coronary Artery Disease Patients

CYP2C19 loss-of-function is associated with increased risk of hypertension in a Hakka population: a case-control study

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