Genetic and phenotypic frequency distribution of CYP2C9, CYP2C19 and CYP2D6 in over 3200 Han Chinese

He, Lin; Chen, Heng; Li, Jingao; Xie, Xiaoxue; Huang, Lihua; Kuang, Yun; Xu, Kangwei; Huang, Wanxia; Zhao, Yanling; Yang, Guoping; Guo, Chengxian

doi:10.1111/1440-1681.13357

Cited by 16 publications

(14 citation statements)

References 12 publications

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“…The frequency of the NM, IM, PM, and UM phenotypes was 48.22%, 42.98%, 6.64%, and 2.16% respectively. Notably, a similar trend was observed for the IM among the Thais and Han Chinese in previous studies 20 , 31 . The CYP2C19 metabolic phenotypes are uniformly distributed across African-American, Asian, Caucasian, Hispanic, and Ashkenazi Jewish populations 30 .…”

Section: Discussionsupporting

confidence: 87%

“…Concerning the metabolic predicted phenotypes, the frequencies of CYP2C9 IM and PM were 10.37% and 0.17%, respectively. Interestingly, these frequencies were more consistent with the Han Chinese population (8.23% IM and 0.16% PM) 20 . The Clinical Pharmacogenetics Implementation Consortium (CPIC) has published recommendations for pharmacogenetic testing on the CYP2C9 gene for dosing of phenytoin, (NSAIDs), and warfarin 21 – 23 .…”

Section: Discussionsupporting

confidence: 74%

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Allele frequencies of single nucleotide polymorphisms of clinically important drug-metabolizing enzymes CYP2C9, CYP2C19, and CYP3A4 in a Thai population

Sukprasong

Chuwongwattana

Koomdee

et al. 2021

Sci Rep

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Prior knowledge of allele frequencies of cytochrome P450 polymorphisms in a population is crucial for the revision and optimization of existing medication choices and doses. In the current study, the frequency of the CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP2C19*6, CYP2C19*17, and CYP3A4 (rs4646437) alleles in a Thai population across different regions of Thailand was examined. Tests for polymorphisms of CYP2C9 and CYP3A4 were performed using TaqMan SNP genotyping assay and CYP2C19 was performed using two different methods; TaqMan SNP genotyping assay and Luminex x Tag V3. The blood samples were collected from 1205 unrelated healthy individuals across different regions within Thailand. Polymorphisms of CYP2C9 and CYP2C19 were transformed into phenotypes, which included normal metabolizer (NM), intermediate metabolizer (IM), poor metabolizer (PM), and rapid metabolizers (RM). The CYP2C9 allele frequencies among the Thai population were 0.08% and 5.27% for the CYP2C9*2 and CYP2C9*3 alleles, respectively. The CYP2C19 allele frequencies among the Thai population were 25.60%, 2.50%, 0.10%, and 1.80% for the CYP2C19*2, CYP2C19*3, CYP2C19*6, and CYP2C19*17 alleles, respectively. The allele frequency of the CYP3A4 (rs4646437) variant allele was 28.50% in the Thai population. The frequency of the CYP2C9*3 allele was significantly lower among the Northern Thai population (P < 0.001). The frequency of the CYP2C19*17 allele was significantly higher in the Southern Thai population (P < 0.001). Our results may provide an understanding of the ethnic differences in drug responses and support for the utilization of pharmacogenomics testing in clinical practice.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 74%

Allele frequencies of single nucleotide polymorphisms of clinically important drug-metabolizing enzymes CYP2C9, CYP2C19, and CYP3A4 in a Thai population

Sukprasong

Chuwongwattana

Koomdee

et al. 2021

Sci Rep

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“…5 As 1 of the most commonly used PPIs, omeprazole has shown considerable potential for drug interactions, given its high affinity for CYP2C19 and moderate affinity for CYP3A4. 22,23 However, no obvious effect was detected in the present study; this could be attributed to polymorphisms and phenotypic changes of CYP2C19, 24,25 large interindividual variation in cytochrome P450 2C19 (CYP2C19) activity, 26 and the relatively small sample size. The relatively high PK variability of pyrotinib may be related to these enzymes.…”

Section: Discussioncontrasting

confidence: 74%

Clinical study of drug–drug interaction between omeprazole and pyrotinib after meal

Wang

Zhu

et al. 2021

Brit J Clinical Pharma

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Aims We aimed to investigate the effect of omeprazole on the pharmacokinetics (PK) of pyrotinib and determine the safety of this combination in healthy Chinese volunteers. Methods Eighteen healthy volunteers were enrolled in this single‐dose and self‐controlled study. Pyrotinib (400 mg per oral) was administered 30 minutes after the standard meal. Omeprazole was administered from day 6 (D6) to D10 (40 mg, per oral). On D10, the subjects took omeprazole under fasting conditions, followed by pyrotinib 30 minutes after the standard meal. Blood samples for PK analyses in each phase were collected for analysing the drug concentration. Safety was assessed via clinical laboratory tests and physical examinations. Results Compared with a single dose of pyrotinib, pyrotinib coadministered with omeprazole showed no significant difference in exposure, elimination, half‐life and apparent clearance rate. The mixed‐effects model revealed that the least‐squares geometric mean ratios of area under the concentration–time curve (AUC)0‐t, AUC0‐∞ and maximum plasma concentration (Cmax,90% confidence intervals) of pyrotinib alone and pyrotinib coadministered with omeprazole were 0.94 (0.82, 1.08), 0.94 (0.83, 1.08) and 0.91 (0.806, 1.038), respectively, indicating the absence of significant differences in AUC0‐t, AUC0‐∞ and Cmax. During the treatment period, 6 subjects (33.3%) reported 8 adverse events during pyrotinib monotherapy and omeprazole administration, respectively; 10 subjects (55.6%) reported 34 adverse events in the combined administration phase. Conclusion Omeprazole, a proton‐pump inhibitor, did not significantly impact the PK properties of pyrotinib, and a good safety profile was observed on coadministration.

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“…Importantly, a genotype frequency of 0.29% for mutant-type homozygotes CYP2C9*3/*3 was noticed in the hypertensive patients, whereas CYP2C9*3/*3 genotype was not detected in the normotensive Han population. On the contrary, one recent research has indicated that the frequency of CYP2C9*3/*3 is 0.1% in the normotensive Han population [20]. These inconsistent conclusions may be due to different samples sizes.…”

Section: Discussionmentioning

confidence: 91%

Distributive characteristics of the CYP2C9 and AGTR1 genetic polymorphisms in Han Chinese hypertensive patients: a retrospective study

Chen

Xiao

Li³

et al. 2021

BMC Cardiovasc Disord

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Background There is an individual variation in response to antihypertensive effect of the angiotensin II receptor antagonist. This study aimed to determine the allele and genotype frequencies of CYP2C9 and AGTR1 genetic polymorphisms and explore the potential role of these polymorphisms in guiding the selection of angiotensinIIreceptor antagonist in Han Chinese hypertensive patients. Methods Totally 2419 Han Chinese hypertensive patients and 126 normotensive controls were recruited in this study. Venous blood samples were collected from each patient, and the genetic polymorphisms of CYP2C9 and AGTR1 were assessed using a gene chip platform. The allele and genotype frequency of each gene and the combined genotypes in this study were analyzed respectively. Results The gene chip analysis identified an allelic frequency of 96.51% for CYP2C9*1 and 3.49% for CYP2C9*3 in the cohort of Han Chinese hypertensive patients. Statistical analysis showed that the frequency of wild-type homozygous for CYP2C9*1/*1 was 93.30%, while the frequency of heterozygous for *1/*3 or mutant homozygous for *3/*3 was 6.41% or 0.29%. Meanwhile, we detected allelic frequencies of 95.06% and 4.94% for the A and C allele of AGTR1, respectively. While the genotype frequency of wild-type homozygous for AA was 90.41%, the frequency of heterozygous for AC or mutant homozygous for CC was 9.30% or 0.29%. Notably, we observed that 84.66% (2048/2419) of the subjects exhibited a combined genotype of CYP2C9 and AGTR1 as *1/*1 + AA, while the combined genotypes *3/*3 + AC or *3/*3 + CC were not detected in hypertension patients. Besides, no significant association was found between normotensive controls and hypertensive patients, or among the three grades of hypertensive patients. Conclusions These data revealed the polymorphisms characteristics of CYP2C9 and AGTR1 in Han Chinese hypertensive patients, providing valuable information for genotype-based antihypertension therapy in prospective clinical studies in the future.

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Genetic and phenotypic frequency distribution of CYP2C9, CYP2C19 and CYP2D6 in over 3200 Han Chinese

Cited by 16 publications

References 12 publications

Allele frequencies of single nucleotide polymorphisms of clinically important drug-metabolizing enzymes CYP2C9, CYP2C19, and CYP3A4 in a Thai population

Allele frequencies of single nucleotide polymorphisms of clinically important drug-metabolizing enzymes CYP2C9, CYP2C19, and CYP3A4 in a Thai population

Clinical study of drug–drug interaction between omeprazole and pyrotinib after meal

Distributive characteristics of the CYP2C9 and AGTR1 genetic polymorphisms in Han Chinese hypertensive patients: a retrospective study

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