Effects of CYP2C19*2 polymorphisms on the efficacy and safety of phenazepam in patients with anxiety disorder and comorbid alcohol use disorder

Introduction: Phenazepam therapy can often be ineffective and some patients develop dose-related adverse drug reactions. Aim. The purpose of this research was to study the effect of the CYP2C19*2 (681G>A, rs4244285) in patients with anxiety disorders and alcohol dependence taking phenazepam therapy. Materials & methods: Patients (175 males, average age: 37.16 ± 7.84 years) received phenazepam in tablet form for 5 days. Genotyping was performed by real-time polymerase chain reaction. Results: The statistically significant differences in the UKU Side-Effect Rating Scale scores on the fifth day of therapy: ( CYP2C19*1/*1) 2.00 [1.00; 2.00), ( CYP2C19*1/*2) 7.00 (7.00; 7.00), ( CYP2C19*2/*2) 9.00 (8.00; 9.00), p < 0.001. Conclusion: This study demonstrated the different efficacy and safety of phenazepam in patients with different genotypes of CYP2C19*2.

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Effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0177 ◽

2019 ◽

Vol 97 (8) ◽

pp. 781-785 ◽

Cited By ~ 2

Author(s):

M.S. Zastrozhin ◽

V.Y. Skryabin ◽

V.V. Smirnov ◽

E.A. Grishina ◽

K.A. Ryzhikova ◽

...

Keyword(s):

Alcohol Use ◽

High Performance ◽

Alcohol Use Disorder ◽

Depressive Disorders ◽

Rating Scale ◽

Correlation Coefficients ◽

Inverse Correlation ◽

Efficacy And Safety ◽

Cyp2d6 Activity ◽

Scale Scores

The objective of the study was to investigate the effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder who received mirtazapine. The study included 109 Russian patients who received mirtazapine at a dose of 30.0 [15.0; 45.0] mg per day. Genotyping of CYP2D6*4 (1846G > A, rs3892097) was performed using real-time polymerase chain reaction with allele-specific hybridization. The activity of CYP2D6 was evaluated by determining the concentration of endogenous substrate of the enzyme and its urinary metabolite — pinoline to 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline ratio, using high-performance liquid chromatography – mass spectrometry. The statistically significant differences between the scores on the Hamilton Depression Rating Scale (HAMD) in patients with different genotypes were revealed by day 16: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [1.0; 3.2] (p < 0.001), and for the The UKU Side Effects Rating Scale (UKU): (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p < 0.001). The calculation of correlation coefficients between the differences in scale scores and metabolic rate showed the presence of statistically significant weak inverse correlation with the efficacy indicator evaluated by HAMD (r = −0.278, p < 0.05), but not by UKU (r = 0.274, p > 0.05). This study demonstrated that an increased CYP2D6 activity reduces the efficacy of treatment with mirtazapine.

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Analysis by rotavirus gene 6 reverse transcriptase-polymerase chain reaction assay of rotavirus-positive gastroenteritis cases observed during the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST)

Human Vaccines & Immunotherapeutics ◽

10.4161/hv.29176 ◽

2014 ◽

Vol 10 (8) ◽

pp. 2267-2275 ◽

Cited By ~ 5

Author(s):

David O Matson ◽

Timo Vesikari ◽

Penelope Dennehy ◽

Michael D Dallas ◽

Michelle G Goveia ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Reverse Transcriptase ◽

Polymerase Chain Reaction Assay ◽

Efficacy And Safety ◽

Chain Reaction ◽

Polymerase Chain

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

Drug Metabolism and Personalized Therapy ◽

10.1515/dmpt-2019-0020 ◽

2019 ◽

Vol 34 (4) ◽

Author(s):

Palden Wangyel Dorji ◽

Sonam Wangchuk ◽

Kanyarat Boonprasert ◽

Mayuri Tarasuk ◽

Kesara Na-Bangchang

Keyword(s):

Polymerase Chain Reaction ◽

Fragment Length Polymorphism ◽

Allele Frequencies ◽

Drug Reactions ◽

Pharmacological Treatments ◽

Chain Reaction ◽

East Asians ◽

Genotype Frequencies ◽

Polymerase Chain ◽

Restriction Fragment Length

Abstract 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.

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The polymorphic variants DRD2, DRD3, and DRD4 are associated with early efficacy and safety of antipsychotics in adolescents with an acute psychotic episode

Clinical pharmacology and therapy ◽

10.32756/0869-5490-2021-2-75-80 ◽

2021 ◽

Vol 30 (2) ◽

pp. 75-80

Author(s):

D.V. Ivaschenko ◽

L.V. Fedina ◽

D.A. Yudelievich ◽

N.I. Buromskaya ◽

P.V. Shimanov ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Observational Study ◽

Prospective Observational Study ◽

Psychotic Episode ◽

Efficacy And Safety ◽

Chain Reaction ◽

Polymorphic Variants ◽

Polymerase Chain ◽

Time Of Admission

The prospective observational study included 101 adolescents diagnosed with acute polymorphic psychotic disorder at the time of admission. Patients were followed up for 14 days. All patients received an antipsychotic as their main therapy. The following scales were used to assess the efficacy and safety of therapy on day 14: CGAS, PANSS, CGI-S, CGI-I, UKU SERS, SAS, BARS. The determination of polymorphic variants of DRD2 (rs1800497, C>T), DRD3 (rs6280, C>T), DRD3 (rs324026, C>T), and DRD4 (rs1800955, C>T) genes was performed by real-time polymerase chain reaction (PCR).

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Comprehensive assessment of variants of cytochrome system, APOE and SLCO1B1 genes, potentially affecting the action of statins

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.05.71-73 ◽

2020 ◽

pp. 71-73

Author(s):

Е.В. Зятенкова ◽

А.И. Ершова ◽

А.Н. Мешков ◽

А.В. Киселева ◽

М. В. Климушина ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Drug Therapy ◽

Carrier Proteins ◽

Drug Reactions ◽

Pharmacokinetics And Pharmacodynamics ◽

Chain Reaction ◽

Individual Snps ◽

High Prevalence ◽

Polymerase Chain ◽

Cytochrome P 450

Варианты генов в системе цитохрома Р 450, белков-переносчиков играют роль в изменении фармакокинетики и фармакодинамики статинов, что может приводить к снижению эффективности медикаментозной терапии, развитию нежелательных лекарственных реакций. Цель: оценить сочетания вариантов нуклеотидной последовательности (ВНП) генов CYP3A4, CYP3А5, CYP2C9, CYP2C19, CYP2D6, APOE, SLCO1B1, потенциально влияющих на действие статинов, в случайной выборке больных. У 38 случайно отобранных пациентов исследовали 60 ВНП методом полимеразной цепной реакции в реальном времени, используя экспресс-панель TaqMan® OpenArray® PGx (ThermoFisherScientific, США). У всех пациентов был выявлен как минимум один ВНП, связанный с эффективностью статинов. У 39 % выявлены сочетания как минимум двух ВНП, потенциально влияющих на действие статинов. У 25% пациентов выявлены сочетания вариантов CYP2C19 (rs4244285, rs12248560 или rs4986893) и CYP2C9 (rs28371688 или rs1799853). У 13% пациентов выявлены сочетания вариантов CYP3А4 (rs55785340 или rs2740574), CYP3А5 (rs776746) и CYP2D6 (rs5030656, rs1065852, rs28371725 или rs3892097). У 29% выявлены ВНП APOE, потенциально изменяющие эффект статинов. 25% пациентов имели генотип СT rs4149056 гена SLCO1B1. Доля пациентов с генотипом СТ rs4149056 и как минимум двумя ВНП генов, ассоциированных с эффективностью статинов, составила 45%. Ввиду высокой распространенности ВНП генов, участвующих в метаболизме статинов, а также незначительного эффекта одного ВНП, по данным литературы, можно предположить, что для повышения информативности фармакогенетического тестирования при терапии статинами следует изучать влияние не отдельного ВНП, а их сочетаний. Variants of genes in the cytochrome P 450 system and carrier proteins play a role in changing the pharmacokinetics and pharmacodynamics of statins, which can lead to a decrease in the effectiveness of drug therapy and the development of undesirable drug reactions. Aim: to evaluate combinations of SNPs of the CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, APOE, SLCO1B1 genes that potentially affect the action of statins in a random sample of patients. In 38 randomly selected patients, 60 SNP were examined using real-time polymerase chain reaction and TaqMan® OpenArray® PGx (ThermoFisherScientific, США). All patients had at least one SNP associated with the effectiveness of statins. In 39%, combinations of at least two SNPs have been identified that potentially affect the action of statins. In 25% of patients, combinations of CYP2C19 (rs4244285, rs12248560 or rs4986893) and CYP2C9 (rs28371688 or rs1799853) variants were revealed. 13% patients had combinations of CYP3A4 (rs55785340 or rs2740574), CYP3A5 (rs77676746), and CYP2D6 (rs5030656, rs1065852, rs28371725 or rs3892097) variants. All variants except rs776746 were heterozygous. In 29% of patients, APOE SNPs were detected. 25% of patients had the CT genotype rs4149056 of the SLCO1B1 gene. The proportion of patients with CT genotype rs4149056 and at least two SNPs genes associated with statin efficacy was 45%. Due to the high prevalence of SNP genes involved in statin metabolism, as well as the insignificant effect of SNP alone, according to the literature, it can be assumed that in order to increase the informativeness of pharmacogenetic testing in statin therapy, it is necessary to study the effect of not individual SNPs, but their combinations.

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Study on the Efficacy and Safety of Non-Factor Drugs Applied the Etiological Classification for Treatment of Hemophilia:a Multi-Centre, Prospective Single-Arm Clinical Trial

Blood ◽

10.1182/blood.v128.22.4986.4986 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4986-4986

Author(s):

Shanxi Liu ◽

Yanfeng Xiao ◽

Jun Lv ◽

Qingbo Liu ◽

Pengbo Li ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Acute Toxicity ◽

Conflicts Of Interest ◽

Diagnostic Methods ◽

Shanxi Province ◽

Efficacy And Safety ◽

Chain Reaction ◽

Long Distance ◽

Intravenous Drip ◽

Polymerase Chain

Abstract Objective: Research on the efficacy and safety of non-factor drugs applied the etiological classification for treatment of hemophilia. Diagnostic Methods: Between from June 2013 and June 2014, 73 patients were treated because of hemophilia. There were 69 males and 4 females, ages ranging from 0.4 to 83 years, with a mean of 16.13. We used MC-1000 Coagulometer (from MDC,Berlin, Germany) to detect the level of F¢ø/F¢ù:C, and detected the level of F¢ø/F¢ù inhibitor using Nigmegen assay. To detect mutations in the F8 and F9 gene, Intron 22 inversions were studied by inverse-shifting polymerase chain reaction (IS-PCR) and intron 1 inversions by long distance polymerase chain reaction. Point mutations were studied by sequencing the coding and promoter regions of the F8 and F9 genes. Therapeutic Methods: Patients with hemophilia were prospectively treated with Non-factor drugs without replacement therapy of F¢ø/F¢ù factor. Patients with mutations in f8 and f9 genes were treated with orally Compound Hemophilia Capsule (Shaanxi Yida Hemophilia Institute, Pat. No:ZL201410130047X, Shaanxi Drug Approval No.Z20150044). Each capsules contain the traditional Chinese medicine raw materials as shown in the following: Ginseng Radix et Rhizoma 0.035g, Astragali Radix 0.117g, Angelica Sinensis Radix 0.035g, Paeoniae Radix Alba 0.07g, Ligustri Lucidi Fructus 0.058g, Ecliptae Herba 0.058g etc. specification: 0.3g/capsule*40 capsule/bollte. The effect of drugs was to enhance the activity and synthesis of coagulation factors in hepatocyte. The dose of 1.2g for adults administered three times daily from 3 months to 6 months. The LD50 of the drugs is 32g/Kg in the mice's acute toxicity test, which is equivalently to 533 times than the therapeutic dosage. In this study, no acute toxicity were observed. Other patients with normal f8 and f9 genes were treated with three kinds of drugs as shown in the following: Cyclophosphamide Injection (Shanxi Pude Pharmaceutical Co., Ltd, Shanxi province, China, H14023686). The dose of 0.2g for adults administered four-intravenous-drip daily from 4 weeks to 6 weeks. Compound Glycyrthizin Injection (Minophagen Pharmaceutical Co.,Ltd, Eisai China Inc. H20190124). The dose of 0.04g for adults administered four-intravenous-drip daily for 4 weeks. The effect of drugs was to stimulating the proliferation and protecting hepatocyte. Mycophemolate Mofetil Capsule (Cisen Pharmaceutical Co., Ltd. Shandong province. China, H20080764). The dose of 1.0g for adults administered twice daily by oral. The effect of drugs was immunosuppressive. Results: Patients were classified by HA (52 cases, 71.23%, F¢ø:C in 1.94±1.59%) and HB (21 cases, 28.77%, F¢ù:C in 2.13±2.06%). There were 58 patients (79.45%) who were detected mutations with maternally inherited, 5 patients(6.85%) who detected mutations without maternally inherited, and 10 cases(13.70%) who had normal f8 and f9 genes. 20 days later after treatment, the level of F¢ø:C was raised from 1.94±1.59 to 11.85±41.33%(P£¼0.01), and the level of F¢ù:C was raised from 2.13±2.06% to 10.10±19.97%(P£¼0.01). However, the patients with normal f8 and f9 genes had the better curative effects (The results were shown in Table/ Figure). After one year, the level of F¢ø:C was 38.89±63.47% in 21 patients with HA, and the level of F¢ù:C was 17.60±32.16% in 10 patients with HB. None of patients reported adverse effects in clinical trials. Conclusion: Non-factor drugs for treatment of hemophilia could promoted the level of F¢ø/F¢ù:C in varying degrees and reduced symptoms. Therefore, the study could provide a new insight into treatment of hemophilia. Further research was needed to understand the mechanism and curative effect. The Institutional Ethics Committee approved the study (Approval No: 20120319). Registration ID: WHO ICTRP & ChiCTR-OPC-16008561 Disclosures No relevant conflicts of interest to declare.

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High performance Nanogold™-in situ hybridzation and its use in the detection of hybridized and PCR-amplified microscopical preparations

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100166944 ◽

1996 ◽

Vol 54 ◽

pp. 896-897

Author(s):

G. W. Hacker ◽

I. Zehbe ◽

J. Hainfeld ◽

A.-H. Graf ◽

C. Hauser-Kronberger ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Messenger Rna ◽

High Performance ◽

Detection System ◽

Direct Methods ◽

Genetic Alterations ◽

Chain Reaction ◽

Protein Encoding ◽

Polymerase Chain

In situ hybridization (ISH) with biotin-labeled probes is increasingly used in histology, histopathology and molecular biology, to detect genetic nucleic acid sequences of interest, such as viruses, genetic alterations and peptide-/protein-encoding messenger RNA (mRNA). In situ polymerase chain reaction (PCR) (PCR in situ hybridization = PISH) and the new in situ self-sustained sequence replication-based amplification (3SR) method even allow the detection of single copies of DNA or RNA in cytological and histological material. However, there is a number of considerable problems with the in situ PCR methods available today: False positives due to mis-priming of DNA breakdown products contained in several types of cells causing non-specific incorporation of label in direct methods, and re-diffusion artefacts of amplicons into previously negative cells have been observed. To avoid these problems, super-sensitive ISH procedures can be used, and it is well known that the sensitivity and outcome of these methods partially depend on the detection system used.

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