Allele Frequencies Of CYP2C19 Research Articles

Influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation

PurposeWe aimed to investigated the influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT).MethodsThis was a prospective cohort design study. High-performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentration. First-generation sequencing was performed to detect gene polymorphisms. Indicators of liver function were detected at least once before and after voriconazole therapy.ResultsForty-one patients were included in this study, among which, 15 patients (36.6%) had voriconazole-induced liver injury. The proportion of voriconazole trough concentration > 5.5 μg·mL−1 patients within the DILI group (40.0%) was significantly higher compared to the control group (15.4%) (p < 0.05). After administration of voriconazole, the values of ALT (103.3 ± 80.3 U/L) and AST (79.9 ± 60.6 U/L) in the DILI group were higher than that in the control group (24.3 ± 24.8 and 30.4 ± 8.6 U/L) (p < 0.05). There was no significant difference between the two groups in genotype and allele frequencies of CYP2C19*2, CYP2C19*3, CYP2C19*17, and UGT1A4 (rs2011425) (p > 0.05).ConclusionThere was a significant correlation between voriconazole-induced liver injury and voriconazole trough concentration in high-risk Uygur pediatric patients with allogeneic HSCT.

Substantiation of a clopidogrel metabolism-associated gene (CYP2C19) variation among healthy individuals

BackgroundIt is essential to investigate the prevalence of CYP2C19 alleles that affect drug metabolism. This study measures the allelic and genotypic frequencies of CYP2C19 loss-of-function (LoF) alleles CYP2C19∗2, CYP2C19∗3, and gain-of-function (GoF) alleles CYP2C19∗17 in the general population. MethodologyThe study involved 300 healthy subjects between the ages of 18 and 85 recruited by simple random sampling. Allele-specific touchdown PCR was employed to identify the various alleles. The genotype and allele frequencies were calculated and checked for Hardy–Weinberg equilibrium. The phenotypic prediction of ultra-rapid metabolizer (UM = ∗17/∗17), extensive metabolizer (EM = ∗1/∗17, ∗1/∗1), intermediate metabolizer (IM = ∗1/∗2, ∗1/∗3, ∗2/∗17) and poor metabolizer (PM = ∗2/∗2, ∗2/∗3, ∗3/∗3) was made based on their genotype. ResultsThe allele frequency of CYP2C19∗2, CYP2C19∗3, and CYP2C19∗17 was 0.365, 0.0033, and 0.18, respectively. The IM phenotype predominated with an overall frequency of 46.67%, including 101 subjects with ∗1/∗2, two subjects with ∗1/∗3, and 37 subjects with ∗2/∗17 genotype. This was followed by EM phenotype with an overall frequency of 35%, including 35 subjects with ∗1/∗17 and 70 subjects with ∗1/∗1 genotype. PM phenotype had an overall frequency of 12.67%, including 38 subjects with ∗2/∗2 genotype, and UM phenotype had an overall frequency of 5.67%, including 17 subjects with ∗17/∗17 genotype. ConclusionGiven the high allelic frequency of PM in the study population, a pre-treatment test to identify the individual's genotype may be recommended to decide the dosage, monitor the drug response, and avoid adverse drug reactions.

The frequency of major ABCG2, SLCO1B1 and CYP2C9 variants in Asian, Native Hawaiian and Pacific Islander women subgroups: implications for personalized statins dosing.

Aim: The frequencies of SLCO1B1*5 and CYP2C9*2 and *3 in specific Asian, Native Hawaiian and Pacific Islander (NHPI) subgroups are unknown. Patients & methods: Repository DNA samples from 1064 women self-identifying as Filipino, Korean, Japanese, Native Hawaiian, Marshallese or Samoan and aged 18years or older were used for targeted sequencing of three genetic variants (rs4149056, rs1799853 and rs1057910). Results: SLCO1B1*5 was significantly less frequent in NHPI women (0.5-6%) than in Europeans (16%). Except for Koreans, CYP2C9*2 (0-1.4%) and *3 (0.5-3%) were significantly less frequent in all subgroups than in Europeans (8 and 12.7%, respectively). Prior reports showed that Asian and NHPI individuals have significantly higher ABCG2 Q141K allele frequency (13-46%) than Europeans (9.4%). Combined phenotype rates for rosuvastatin and fluvastatin revealed that Filipinos and Koreans had the highest frequencies of statin-associated myopathy symptoms risk alleles. Conclusion: Differences in ABCG2, SLCO1B1 and CYP2C9 allele frequencies among different racial and ethnic subgroups highlight the need for increased diversity in pharmacogenetic research. Risk alleles for statin-associated myopathy symptoms are more prevalent in Filipinos, underscoring the importance of genotype-based statin dosing.

The frequency of major CYP2C19 genetic polymorphisms in women of Asian, Native Hawaiianand Pacific Islander subgroups.

Aim: Prevalence of clinically actionable genetic variants of CYP2C19 is lacking in specific population subgroups. This study aims to assess the frequencies of CYP2C19*2, *3, and *17 in Asian, Native Hawaiian and Pacific Islander (NHPI) population subgroups compared with Europeans. Patients & methods: The study included repository DNA samples of 1064 women, 18 years or older, who self-reported as Filipino, Korean, Japanese, Native Hawaiian, Marshallese and Samoan. Results: The overall frequencies of CYP2C19*2 (25-36%) and CYP2C19*3 (2.5-10%) were significantly higher in all our subgroups than in Europeans (15 and 0.02%, respectively). The overall frequency of CYP2C19*17 was significantly lower in all our subgroups (1-6%) than in Europeans (21.7%). Conclusion: This is the first report on the frequencies of CYP2C19*2, *3, and *17 in women of Asian and NHPI descent with distinct population subgroup differences. Differential allele frequencies of CYP2C19 among population subgroups underscore the importance of increasing racial and ethnic diversity in pharmacogenetic research.

CYP2C9*3 Increases the Ibuprofen Response of Hemodynamically Significant Patent Ductus Arteriosus in the Infants with Gestational Age of More Than 30 Weeks.

The online version contains supplementary material available at 10.1007/s43657-021-00028-9.

The Frequencies of Allele Distribution of CYP2C9 and CYP2C19 Gene Polymorphisms in Healthy Papuan Population, Indonesia

This study's objective was to determine the distribution of allele frequencies of CYP2C9 and CYP2C19 gene polymorphisms among the Papuan population, known as the second-largest ethnic group in Indonesia. According to recent research, there is a decrease in CYP2C9 and CYP2C19 produced by humans globally, including in Indonesia. These gene polymorphisms aid in the transmission of various endogenous and exogenous drugs in the human body. Material and Methods: A sum of 99 subjects, comprising 73 male and 26 female subjects aged 20-30 years, were used for this research. PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) analysis using AvaII, NsiI, and SfaNI enzymes tested for the genotypes CYP2C9 and CYP2C19 administered. The distribution of genotypes was calculated in the population (P&lt;0.05) using the Hardy-Weinberg equilibrium. The Faculty of Medicine Gadjah Mada University's Medical and Health Research Ethics Committee (MHREC) accepted this research with written consent. The results revealed that in Papua subjects, CYP2C9*2 (rs1799853) and CYP2C19*17 (rs12248560) alleles were absent while in 17 percent of the population CYP2C9*3 (rs1057910) allele frequency was. In conclusion, CYP2C9*3 has the highest polymorphism rate in Indonesia, with the absence of CYP2C9*2 and CYP2C19*17. Therefore, genetic drift can occur within this ethnic group. Keywords: Genotyping; Papuan ethnic; Pharmacogenetics; Polymorphisms

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

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.

Cytochrome P450 2C19 gene polymorphisms (CYP2C19*2 and CYP2C19*3) in chronic myeloid leukemia patients: in vitro and in silico studies

Polymorphisms in the CYP2C19 have a huge impact on drug processing, out of which CYP2C19*2 and CYP2C19*3 are the most common variants associated with reduced metabolism of drugs. Mechanism by which two variants contribute in poor metabolization of drugs and cancer is not well understood. Here, we hypothesized that the mutations in CYP2C19 gene might affect the risk of chronic myeloid leukemia patients (CML). Present study has two main objectives: first to investigate the allele frequencies of CYP2C19*2 and CYP2C19*3 associated gene polymorphisms in CML patients and to elucidate the structural stability, conformation and functions of protein encoded by such variants. Genotyping of CYP2C19 was performed in 103 CML patients and 103 matched healthy controls. Heterozygous genotype of CYP2C19*2 was higher in CML patients (13.59%) than the controls (4.85%). Whereas, CYP2C19*3 allele frequency was not observed in cases as well as in controls. Furthermore, molecular dynamics (MD) simulation was applied to monitor the structural and conformational effect of above mutants. MD simulation results demonstrated that these mutants formed unstable proteins with distorted conformations, altered residues network and affected drug binding site which led to malfunction of mutant proteins. Hence, the study provides the role of CYP2C19 gene polymorphisms in susceptibility to CML population and explored the molecular basis of malignancies caused which may aid in the development of precise medicine or adjusting the drug dosages so as to reduce the chemotherapeutic side effects. Communicated by Ramaswamy H. Sarma

Differences in Predicted Warfarin Dosing Requirements Between Hmong and East Asians Using Genotype-Based Dosing Algorithms.

Warfarin's narrow therapeutic index and high variability in dosage requirements make dosage selection critical. Genetic factors are known to impact warfarin dosage selection. The Hmong are a unique Asian subpopulation numbering over 278,000 in the United States whose participation in genetics-based research is virtually nonexistent. The translational significance of early reports of warfarin pharmacogene differences in Hmong has not been evaluated. (i) To validate previously identified allele frequency differences relevant to warfarin dosing in Hmong versus East Asians and (ii) to compare predicted warfarin sensitivity and maintenance doses between a Hmong population and an East Asian cohort. DNA collected from two independent cohorts (n=236 and n=198) of Hmong adults were genotyped for CYP2C9 (*2, *3), VKORC1 (G-1639A), and CYP4F2 (*3). Allele frequencies between the combined Hmong cohort (n=433) and East Asians (n=1165) from the 2009 International Warfarin Pharmacogenetics Consortium (IWPC) study were compared using a χ2 test. Percentages of Hmong and East Asian participants predicted to be very sensitive to warfarin were compared using a χ2 test, and the predicted mean warfarin maintenance dose was compared with a t test. The allele frequencies of CYP2C9*3 in the combined Hmong cohort and CYP4F2*3 in the VIP-Hmong cohort are significantly different from those in East Asians (18.9% vs 3.0%, p<0.001 and 9.8% vs 22.1%, p<0.001, respectively). Comparing the combined Hmong cohort to the East Asian cohort, the percentage of participants predicted to be very sensitive to warfarin was significantly higher (28% vs 5%, p<0.01) and the mean predicted warfarin maintenance dose was significantly lower (19.8 vs 21.3mg/week, p<0.001), respectively. The unique allele frequencies related to warfarin when combined with nongenetic factors observed in the Hmong translate into clinically relevant differences in predicted maintenance dose requirements for Hmong versus East Asians.

Impact of CYP2C19, CYP3A4, ABCB1, and FMO3 genotypes on plasma voriconazole in Thai patients with invasive fungal infections.

Voriconazole is the first‐line antifungal choice in the treatment of invasive fungal infections (IFIs). Single nucleotide polymorphisms (SNPs) in drug‐metabolizing and transporter genes may affect voriconazole pharmacokinetics. This study aimed to determine the frequency of the CYP2C19 rs4244285, rs4986893, rs72552267, and rs12248560, CYP3A4 rs4646437, ABCB1 rs1045642, and FMO3 rs2266782 alleles and determine the association between these genetic variants and voriconazole concentrations in Thai patients with invasive fungal infections. The study comprised 177 Thai patients with IFIs in whom seven SNPs in CYP2C19, CYP3A4, ABCB1, and FMO3 were genotyped using TaqMan real‐time polymerase chain reaction (RT‐PCR) 5´ nuclease assays, and voriconazole plasma concentrations were measured by high‐performance liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Of the 177 patients included, 31 were <12 years and 146 were ≥12 years. The CYP2C19 allele frequencies were 0.29 for *2, 0.060 for *3, 0.003 for *6, and 0.008 for *17. The allele frequency of CYP3A4 (rs4646437) was 0.26, ABCB1 (rs1045642) was 0.36, and FMO3 (rs2266782) was 0.16. The median voriconazole dose/weight was significantly lower in patients aged ≥12 years when compared to the patients aged <12 years (P < .001). Patients aged <12 years with CYP2C19*1/*2 exhibited significantly higher median voriconazole plasma concentrations than those with the CYP2C19*1/*1 (P = .038). However, there were no significant differences in median voriconazole plasma concentrations among the CYP2C19 genotypes in the patients aged ≥12 years. There was a lack of association observed among the CYP3A4, ABCB1, and FMO3 genotypes on the plasma voriconazole concentrations in both groups of patients. Our findings indicate that voriconazole plasma concentrations are affected by the CYP2C19*2 allele in patients aged <12 years but not in patients aged ≥12 years.

Effect of CYP2C19 polymorphism on the plasma voriconazole concentration and voriconazole-to-voriconazole-N-oxide concentration ratio in elderly patients.

Effects of CYP2C19 polymorphism on voriconazole concentration (C0 ), dose-adjusted trough concentrations (C0 /dose) and voriconazole-to-voriconazole-N-oxide concentration ratio (C0 /CN ) have not been fully investigated. To investigate correlations of CYP2C19 polymorphisms with plasma concentrations of voriconazole and the major metabolite voriconazole-N-oxide in elderly patients. A prospective, multi-centre, non-intervention, open clinical study was conducted within Southwestern Chinese patients clinically diagnosed with invasive fungal infections, to investigate the associations of CYP2C19∗2 (681G>A), CYP2C19∗3 (636G>A) and CYP2C19∗17 (-806C>T) genetic polymorphisms with voriconazole C0 , C0 /dose and C0 /CN . The study included 131 adult patients, of which 72 were elderly (≥60years) and 59 were adults (<60years). The allele frequencies of CYP2C19∗2, ∗3 and ∗17 in the elderly cohort were 61.1%, 29.9% and 7.6%, respectively, which were similar to those in the adult cohort (66.9%, 29.7% and 2.5%, respectively; P>.05). The median voriconazole C0 (C0 ), C0 /dose and C0 /CN ratio in patients with the CYP2C19∗1/∗2 and CYP2C19∗2/∗2 genotypes were significantly higher than those in patients with the CYP2C19∗1/∗1 genotype in the adult cohort (P<.05). The C0 and C0 /dose in patients with the CYP2C19∗1/∗3 and CYP2C19∗2/∗2 genotypes, and the C0 /CN ratio for patients with the CYP2C19∗1/∗2 genotype were numerically higher than those in patients with the CYP2C19∗1/∗1 genotype in the elderly cohort, but this difference was not statistically significant (P>0.05). The C0 , C0 /dose and C0 /CN in patients with poor metaboliser phenotypes were higher than in those with normal metaboliser phenotypes and C0 in patients with intermediate metaboliser phenotypes were significantly higher than in those with normal metaboliser phenotypes in the adult cohort (P<.05). However, there were no significant differences in the C0 , C0 /dose and C0 /CN among different CYP2C19-predicted metabolic phenotypes in the elderly cohort. Voriconazole C0 , C0 /dose and C0 /CN ratio are not significantly affected by the CYP2C19∗2/∗3 polymorphisms in the elderly patients.

CYP2C19 Allele Frequencies in Over 2.2 Million Direct-to-Consumer Genetics Research Participants and the Potential Implication for Prescriptions in a Large Health System.

Understanding the prevalence of clinically relevant pharmacogenetic variants using large unselected populations is critical for gauging the potential clinical impact of widespread preemptive pharmacogenetic testing. To this end, we assessed the frequencies and ethnic distribution of the three most common CYP2C19 alleles (*2, *3, and *17) in 2.29 million direct‐to‐consumer genetics research participants (23andMe, Sunnyvale, CA). The overall frequencies of *2, *3, and *17 were 15.2%, 0.3%, and 20.4%, respectively, but varied by ethnicity. The most common variant diplotypes were *1/*17 at 26% and *1/*2 at 19.4%. The less common *2/*17, *17/*17, and *2/*2 genotypes occurred at 6.0%, 4.4%, and 2.5%, respectively. Overall, 58.3% of participants had at least one increased‐function or no‐function CYP2C19 allele. To better understand how this high frequency might impact a real patient population, we examined the prescription rates (Rx) of high‐pharmacogenetic‐risk medications metabolized by CYP2C19 using the University of California at San Francisco (UCSF) health system’s anonymized database of over 1.25 million patients. Between 2012 and 2019, a total of 151,068 UCSF patients (15.8%) representing 5 self‐reported ethnicities were prescribed one or more high‐pharmacogenetic‐risk CYP2C19 medications: proton pump inhibitors (145,243 Rx), three selective serotonin reuptake inhibitor antidepressants (54,463 Rx), clopidogrel (14,376 Rx), and voriconazole (2,303 Rx).

Interethnic differences in the prevalence of main cardiovascular pharmacogenetic biomarkers.

Background: The aim of this study was to determine the prevalence of CYP2C9, VKORC1, CYP2C19, ABCB1, CYP2D6 and SLCO1B1 genes polymorphisms among residents of the Volga region (Chuvash and Mari) and northernCaucasus (Kabardins and Ossetians). Materials & methods: The study involved 845 apparently healthy volunteers of both sexes of the four different ethnic groups living in the Russian Federation: 238 from the Chuvash ethnic group, 206 Mari, 157 Kabardins and 244 Ossetians. Results: Significant differences were identified in allele frequency of CYP2C9, VKORC1, CYP2C19, ABCB1, CYP2D6 and SLCO1B1 genes polymorphisms between the Chuvash and Kabardins, Chuvash and Ossetians, Mari and Kabardians, Mari and Ossetians.

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

Background Marked differences among genotype frequencies (Caucasians, Asians, and Africans) have been observed in cytochrome P450 (CYP) genes. Data on the frequency of pharmacogenetic relevant polymorphisms in Bhutanese population is absent. This study aimed to investigate the frequencies of pharmacogenetic relevant polymorphisms of CYP2C9 (*2 and *3), CYP2C19 (*2 and *3), CYP2D6 (*10), and CYP3A5 (*3) in Bhutanese population. Methods Genotyping was performed in 443 DNA samples using polymerase chain reaction-restriction fragment length polymorphism. Results For CYP2C9, allele frequencies of *2 and *3 variants were 0.339% and 0%, respectively. For CYP2C19, frequencies of *2 and *3 variants were 30.135% and 15.689%, respectively. Allele frequencies of CYP2D6*10 and CYP3A5*3 were 21.332% and 77.314%, respectively. Allele frequencies of CYP2C9*2 are similar to most Asians while CYP2C9*3 was absent. CYP2C19*2 showed a close resemblance to Japanese and Burmese, while CYP2C19*3 is near to Japanese and Korean. CYP2D6*10 is noticeably lower than other Asians. CYP3A5*3 is similar to East Asians (Chinese, Japanese, and Korean). Conclusions The Bhutanese population is polymorphic for these CYP genes, except for CYP2C9*3. Similar to other populations, genetic testing for these genes may, therefore, be helpful to obtain the benefit from pharmacological treatments and prevent adverse drug reactions.

Association of CYP2C19 and UGT1A4 polymorphisms with voriconazole-induced liver injury.

Aim: This study investigated the association between voriconazole-induced liver injury and gene polymorphisms of CYP2C19 and UGT1A4. Materials & methods: Thirty-eight adult patients who received voriconazole therapy were included in the study. Genotype of CYP2C19 was detected using gene chip hybrid analysis. The UGT1A4 142T>G was genotyped using PCR-RFLP analysis. Results: Ten patients (26.3%) had voriconazole-induced liver injury and were considered as the case group There was no significant difference between the two groups in genotype and allele frequencies of CYP2C19*2 and UGT1A4 142T>G (p > 0.05), however, the GA frequency of CYP2C19 *3 in the drug-induced liver injury case group was higher than that in the control group (p < 0.05). Compared with patients carrying *1/*1 or *1/*2, there was no significant difference in voriconazole trough concentration of the patients with *1/*3 (p > 0.05). Conclusion: There was no significant correlation between voriconazole-induced liver injury and gene polymorphisms of CYP2C19 and UGT1A4.

MGB Block ARMS Real-Time PCR for Diagnosis of CYP2C19 Mutation in a Chinese Population

Background:CYP2C19 is an important genetic factor modulating clopidogrel dose requirement.Objective:Therefore, a simple and economic genotyping method for predicting the clopidogrel dose of patients would be useful in clinical applications.Methods:In this study, the MGB blocker ARMS real-time PCR contained two forward primers, two MGB blockers and a common reverse primer have been used for CYP2C19*2, *3 and *17 substitutions.Results:Results showed that heterozygotes and homozygotes of CYP2C19*2, *3 and *17 could be distinguished by the MGB blocker ARMS real-time PCR successfully. In the Chinese population, patients with allele frequencies of CYP2C19*2, *3, and *17 are 18.43%, 3.03% and 0.76%, respectively.Conclusion:This study indicates that the MGB blocker ARMS real-time PCR will be a simple, economical method for the rapid detection of SNPs in CYP2C19.

Effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirement in Central China Han populations

Purpose: To investigate the frequency of CYP2C9 and vitamin K epoxide reductase complex subunit 1 (VKORC1) and determine the effect of these genetic factors on weekly warfarin dose requirement in Central China Han populations.Methods: A total of 333 hospitalized patients with deep venous thrombosis after minimally invasive surgery were enrolled in this study. Genotypes of VKORC1 and CYP2C9 were analyzed by polymerase chain reaction (PCR)-DNA Chip method. Multiple linear regression analysis was used to explore the impact on weekly warfarin dose requirement.Results: The allele frequencies of VKORC1 -1639 G and VKORC1 -1639 A were 0.105 and 0.895, respectively, whereas no genotype of CYP2C9*1*2, CYP2C9*2*2 and CYP2C9*3*3 were found, and the allele frequencies of CYP2C9*1, CYP2C9*2 and CYP2C9*3 were 0.943, 0.015 and 0.042, respectively. Multiple linear regression analysis indicated that several factors including VKORC1 -1639 G>A, CYP2C9*2, CYP2C9*3, age, body mass index (BMI) and amiodarone use may explain the 47.2 % of individual variations in the weekly warfarin doses requirement.Conclusion: There is no significant difference in the frequency of VKORC1 (-1639 G>A), CYP2C9*2 and CYP2C9*3 compared to those of Asian populations, but there is significant difference when compared with those of Europeans and Caucasians. Considering VKORC1 -1639 G>A, CYP2C9*2, and CYP2C9*3 genetic polymorphisms as well as age, BMI and amiodarone use may explain the 47.2% of individual variations in the weekly warfarin doses requirement..Keywords: Warfarin, CYP2C9, VKORC1, Polymorphism, Body mass index, International normalized ratio

A PCR-lateral flow assay system based on gold magnetic nanoparticles for CYP2C19 genotyping and its clinical applications

Presently, clopidogrel is the standard therapeutic drugs for antiplatelet therapy. Variants in the CYP2C19 gene influence the clinical response of clopidogrel. Thus, the US Food and Drug Administration suggested CYP2C19 genotyping needs to identify before taking medicine. Due to high cost, time consuming, and sophisticated instruments, current single nucleotide polymorphism detection methods are limited in clinical application. In the present study, we established a genotyping method for CYP2C19, which combines amplification refractory mutation system (ARMS)-PCR with a lateral flow assay used gold magnetic nanoparticles (GMNPs) named as PCR-gold magnetic lateral flow assay system (PCR-GoldMag LFA). The PCR products with specific genotype can be explained within 5 minutes, either through visual or by a magnetic reader automatically according to the captured GMNPs probes on the test lines of the LFA strips. The limit of detection of this method is 5 ng of genomic DNA. The PCR-GoldMag LFA system was applied in a clinical trial with 1356 samples of Han Chinese. The concordance rate between the LFA system and sequencing is 99.93%. The allele frequency of CYP2C19*2 and CYP2C19*3 are 30.38 and 7.08% in Han Chinese, respectively. This method provides a new way in the clinical application of CYP2C19 genotyping to guide the clopidogrel medication.

Genotype and Allele Frequencies of CYP2C9, VKORC1, CYP2C19 and PON1 in Chinese Han Population Detected in our Hospital

Warfarin and clopidogrel are commonly used anticoagulant and antiplatelet drugs, and their response and/or toxicity were significant influenced by genetic polymorphism of drug metabolizing enzymes transporters and drug targets...

Characterization CYP1A2, CYP2C9, CYP2C19 and CYP2D6 Polymorphisms Using HRMA in Psychiatry Patients with Schizophrenia and Bipolar Disease for Personalized Medicine.

The interindividual genetic variations in drug metabolizing enzymes effects the impact and toxicity in plenty of drugs. CYP1A2, CYP2C9, CYP2C19 and CYP2D6 gene polymorphisms were characterized using high resolution melting analysis (HRMA) in follow-up patients in psychiatry clinic as a preliminary preparation for personalized medicine. Genotyping of CYP1A2*1F, CYP2C9 *2, *3, CYP2C19 *2, *3 and *17 and CYP2D6 *3, *4 was conducted in 101 patients using HRMA. Genotype and allele frequencies of the CYP variants were found to be in equilibrium with the Hardy-Weinberg equation. The frequency of the CYP1A2*1F allele in schizophrenia and bipolar disease was 0.694 and 0.255, respectively. The CYP2C9 allele frequencies were 0.087 (CYP2C9*2), and 0.549 (CYP2C9*3) for bipolar; 0.278 (CYP2C9*2) and 0.648 (CYP2C9*3) in schizophrenias. The CYP2C19*2 and *17 allele frequencies was 0.111 and 0.185 in schizophrenia and variant *2 was 0.117 and variant *17 was 0.255 in bipolar group. The frequency of the CYP2D6*3 allele was 0.027 in schizophrenias. The frequencies for the CYP2D6*4 variant were 0.092 and 0.096 in schizophrenia and bipolar groups, respectively. The knowledge in pharmacogenomic and also the developments in molecular genetics are growing rapidly. In future, this can be expected to provide new methodologies in the prediction of the activity in drug metabolizing enzymes. The HRMA is a rapid and useful technique to identify the genotypes for drug dosage adjustment before therapy in psychiatry patients.