Analysis on risk factors of clopidogrel resistance in patients with ischemic stroke / 药学实践杂志

Objective To investigate the risk factors of drug resistance in patients with ischemic stroke by clopidogrel therapy and provide references for promoting clinical individualized drug therapy. Methods A total of 202 inpatients diagnosed with ischemic stroke were admitted and given dual anti-treatment (aspirin+clopidogrel). CYP2C19 genotype was detected by microarray hybridization during hospitalization, and CYP2C19 gene polymorphisms were classified into fast metabolism group, medium metabolism group and slow metabolism group according to the type of drug metabolism. Patients were tested for platelet inhibition induced by adenosine diphosphate (ADP) according to thromboelastographic (TEG) on 7~14 d of drug administration. ADP <30% was classified as clopidogrel drug resistance group and ADP ≥30% as non-resistance group. Logistic regression analysis was used to study the risk factors for the development of clopidogrel resistance. Results Among 202 patients with ischemic stroke, 87 were in the resistant group and 115 in the non-resistant group. The proportion of patients with clopidogrel resistance combined with diabetes and the level of white blood cell count were higher than that in the non-resistant group, and the differences were statistically significant (P<0.05).The proportion of patients with clopidogrel resistance in the CYP2C19 intermediate metabolism group was significantly higher than that in the fast metabolism group, and the rate of platelet inhibition was also significantly lower than that in the fast metabolism group, all with statistically significant differences (P<0.05). Conclusion Combined diabetes mellitus, high white blood cell count levels and CYP2C19 mid-metabolic phenotype are independent risk factors for the development of clopidogrel resistance in patients with ischemic stroke.

Effects of single nucleotide polymorphism of drug metabolizing enzyme cytochrome P450 on the efficacy of inhaled cortisol hormone in asthmatic children / 中国临床药理学与治疗学

AIM: To elucidate the relationship between childhood asthma susceptibility and clinical efficacy of inhaled glucocorticoids (ICS) in children with different genotypes of asthma by exploring rs776746 and rs15524 single nucleotide polymorphisms (SNPs) of cytochrome P450 enzyme 3A5 (CYP3A5) gene in asthmatic children and healthy children. METHODS: The CYP3A5 gene rs776746 and rs15524 polymorphic sites were detected in 79 children (Case group) with asthma of Han nationality and 100 healthy children (Control group) who met the inclusion criteria admitted to the Northern Theater General Hospital in Northeast China from October 2016 to October 2020, and genotype, allele and linkage analysis were performed. The case group was given inhaled glucocorticoids by nebulised inhalation for 3 months, and lung function and exhaled breath nitric oxide (FeNO) were measured at entry and after treatment, and asthma control score C-ACT/ACT was done after treatment, so as to compare the prevalence of different genotypes and the differences in the above test index scores. RESULTS: There was complete linkage disequilibrium at rs776746 and rs15524 loci. There were three genotypes of T/T, T/C and C/C at rs776746 locus of CYP3A5 gene. There were significant differences in the frequency of different genotypes between the case group and the control group (χ

Advances in venlafaxine-related PK-PD relationship and influencing factors / 中国临床药理学与治疗学

Venlafaxine (VEN) is a new antidepressant drug that can effectively antagonize the reuptake of serotonin (5-HT) and norepinephrine (NE), compared with other antidepressants, venlafaxine pharmacokinetics / pharmacodynamics (PK-PD) is more regular and has the characteristics of less toxic side effects, fast oral absorption, and high bio-availability. This article reviews the PK-PD model-ling of venlafaxine and its quantitative relationship, as well as the factors affecting the process in vivo of venlafaxine, including sex, body weight, individual genotype, liver and kidney function impairment, drug-drug interaction and other related factors.

Research progress on metabolic activation of indirect carcinogens by CYP1A1 / 中国职业医学

Cytochrome P450 enzyme 1A1 (CYP 1A1) is one of the main members of CYP1A subfamily, which participates in metabolizing and activating a variety of indirect carcinogens. CYP1A1 can induce carcinogenesis by participating in activating exogenous compounds to produce intermediates or active metabolites that bind to specific biomolecules. CYP1A1 plays a critical role in the metabolic activation of benzo(a)pyrene e ［B(a)P］, and plays a key role in activating the toxic and carcinogenic effects of B(a)P. CYP1A1 involves in the metabolic activation of 7,12-dimethyl benzanthracene and 2-amino-1-methyl-6-phenylimidazo［4,5-b］pyridine (PhIP), and plays an important role in PhIP-induced genotoxicity. CYP1A1 is the main enzyme to metabolize and activate 7H-dibenzo［c,g］carbazole (DBC), a key factor in the carcinogenic effect of DBC. CYP1A1 is also associated with metabolic activation of indirect carcinogens such as aflatoxin B1, 3-nitrobenzene, and naphthalene. Inhibition of the catalytic activity of CYP1A1 can decrease the CYP1A1-mediated activity of carcinogens, thus playing a role in the prevention and treatment of malignant tumors.

Cytochrome P450 oxidoreductase deficiency in an infant / 中华围产医学杂志

This study reported the diagnosis and treatment of cytochrome P450 oxidoreductase deficiency (PORD) in a male infant. The patient was admitted to Children's Hospital Affiliated to Shandong University at the age of 38 days due to nasal obstruction and feeding difficulties presented at 10 d after birth, as well as less weight gain. Physical examination showed craniosynostoses, hand and foot deformities, and normal external genitalia. Laboratory examination revealed mildly elevated serum adrenocorticotrophic hormone and decreased level of baseline cortisol. A homozygous mutation of c.1370G>A(p.R457H) in POR gene was detected by whole-exome sequencing, which confirmed the diagnosis of PORD. Skeletal deformities complicated by external genital malformations and/or adrenocortical hormone abnormalities are important diagnostic indicators for PORD.

Role of the cytochrome P450 family in metabolic-associated liver diseases / 临床肝胆病杂志

The cytochrome P450 (CYP) family is the most important drug-metabolizing enzyme in human body and is responsible for the metabolism of endogenous and exogenous compounds. As the main site of the expression of the CYP family, the liver is the metabolic center of drugs, and in recent years, the role of the CYP family in the liver has attracted wide attention from the scholars in China and globally. This article reviews the distribution differences of the CYP family from the aspects of anatomy, genetics, and genomics, changes in the expression of the CYP family in the pathological processes such as non-alcoholic fatty liver disease, alcoholic liver disease, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma, and the effect of CYP family-mediated enzyme activity on the treatment effect of pharmacotherapy for metabolic-associated liver diseases, in order to provide important enlightenment for identifying key drug intervention targets in diseases and enhancing clinical efficacy and safety.

Analysis and clinical significance of cytochrome P 450 2C19 gene in patients with cardiovascular and cerebrovascular diseases in southern Yunnan / 中国基层医药

Objective:To analyze the distribution and clinical significance of cytochrome P 450 2C19 (CYP2C19) gene in patients with cardiovascular and cerebrovascular diseases in southern Yunnan. Methods:The data of 245 patients with cardiovascular and cerebrovascular diseases who received treatment in Southern Central Hospital of Yunnan Province between May 2019 and June 2020 were retrospectively analyzed. The distribution of CYP2C19 gene and its relationship with nationality, age, sex, blood lipids, hypertension, and diabetes were analyzed and compared between southern Yunnan and other regions.Results:The proportions of seven phenotypes of CYP2C19 gene *1/*17, *1/*1, *1/*2, *1/*3, *2/*2, *2/*3, *3/*3 in 245 patients were 2.86%, 38.37%, 39.18%, 5.31%, 9.39%, 4.08% and 0.82%, respectively. The proportions of individuals with superfast/ultrafast metabolism, fast metabolism, intermediate metabolism, and slow metabolism in 245 patients were 2.86%, 38.37%, 44.49%, and 14.29%, respectively. The frequency of polymorphisms in the CYP2C19 gene was consistent with the Hardy-Weinberg equilibrium ( P > 0.05), which was constant and representative. The Fisher test showed that the CYP2C19 gene distribution of patients with cardiovascular and cerebrovascular diseases in southern Yunnan was not greatly correlated with nationality, age, sex, underlying disease, blood lipids, and the types of cardiovascular and cerebrovascular diseases (all P > 0.05). There was a significant difference in CYP2C19 gene distribution in patients from southern Yunnan versus Dongguan, Jiangxi, Fujian, northern Sichuan, Chifeng, Xiamen, Shaanxi, and Kunming ( P < 0.001, < 0.001, 0.045, 0.008, 0.001, 0.005, < 0.001, 0.016). Conclusion:The distribution of CYP2C19 gene in patients with cardiovascular and cerebrovascular diseases in southern Yunnan is not obviously correlated with nationality, age, sex, underlying diseases, blood lipids, and the types of cardiovascular and cerebrovascular diseases. CYP2C19 gene distribution is related to regional distribution, which can guide personalized medication in different regions.

A review: biosynthesis of plant-derived labdane-related diterpenoids / 中国天然药物

Plant-derived labdane-related diterpenoids (LRDs) represent a large group of terpenoids. LRDs possess either a labdane-type bicyclic core structure or more complex ring systems derived from labdane-type skeletons, such as abietane, pimarane, kaurane, etc. Due to their various pharmaceutical activities and unique properties, many of LRDs have been widely used in pharmaceutical, food and perfume industries. Biosynthesis of various LRDs has been extensively studied, leading to characterization of a large number of new biosynthetic enzymes. The biosynthetic pathways of important LRDs and the relevant enzymes (especially diterpene synthases and cytochrome P450 enzymes) were summarized in this review.

Hepatotoxicity of Main Components of Polygonum multiflorum and Its Effects on Drug Metabolism Enzyme / 中国药房

OBJECTIVE：To study the hepatotoxicity of main components of Polygonum multiflorum ，and investigate its toxic mechanism based on metabolic enzymes. METHODS ：ADMETlab 2.0 platform was used to forecast the toxic or carcinogenic effects of emodin ，physcion，rhein，stilbene glycoside and gallic acid on liver ，skin and heart. The effects of those components on cytochrome P 450 enzyme system （CYP1A2，CYP2C9，CYP2C19，CYP2D6，CYP3A4）were evaluated. The effects of different concentrations of emodin ，rhein，stilbene glycoside and gallic acid （10，20，40，80 μmol/L）on the survival rate of normal hepatocyte L 02 were detected. The effects of major components of P. multiflorum on the activity of UGT 1A1 enzyme were studied by in vitro reaction system ，using bilirubin as substrate. RESULTS ：Main components of P. multiflorum ，ie. emodin ，physcion， rhein and gallic acid ，showed strong toxic effects on the liver ，while stilbene glycosides possessed weak toxic effects on the liver. Emodin and physcion had strong inhibitory effects on CYP 1A2 and medium inhibitory effects on CYP 2C9，CYP2D6 and CYP3A4；rhein showed medium inhibitory effects on CYP 1A2 and CYP 2C9，while stilbene glycoside and gallic acid possessed weak inhibitory effects on the above enzymes. Emodin （40，80 μmol/L）and gallic acid （40，80 μmol/L）could significantly reduce the survival rate of L 02 cells（P＜0.01）. The inhibition rate of 5，10，20，40，80 μmol/L emodin and gallic acid（except for 5 μmol/L emodin）on UGT 1A1 enzyme increased significantly （P＜0.01），and the inhibition effect of emodin on UGT 1A1 enzyme was reversible competitive inhibition. CONCLUSIONS ：The main components of P. multiflorum ，ie. emodin ，rhein and physcion ， are hepatotoxic ；the mechanism of it may be associated with inhibiting the activity of CYP 1A2 and CYP 2C9 and competitively blocking rate-limiting enzyme UGT 1A1 in the process of bilirubin metabolism.

Immunopharmacology 2020. V International Congress on Immunopharmacology

The Organizing Committee of the V International Congress on Immunopharmacology (Immunopharmacology 2020) organized by the Cuban Society of Pharmacology, BioCubaFarma and the International Union of Basic and Clinical Pharmacology (IUPHAR) would like to invite you to participate in this important event, scheduled for June 9 to 13, 2020 at the Convention Centre of the Melia Marina Varadero Hotel, Varadero Beach, Matanzas, Cuba. The Congress will be formed by different workshops and symposia such as: Fifth workshop on new advances in immunopharmacology Fifth workshop on neuroimmunology, neuroimmunopharmacology and neuroimmunomodulation. Immunopharmacology of brain tumors Symposium on hereditary ataxias Fifth symposium on pharmacology of cytochrome P450 and transporters Fourth symposium on inflammation and pain 2nd symposium on NFkB Synthetic peptides as immunopharmacological tools Novel designs in clinical trials. Biosimilar pharmaceuticals Pharmacogenetics, pharmacogenomics, proteomics and phosphoproteomics Immune response in cancer First symposium on business and international cooperation on biologics Immunopharmacology 2020 is sponsored by: Cuban Society of Pharmacology (SCF) International Union of Basic and Clinical Pharmacology (IUPHAR) Latin-American Association of Pharmacology (ALF) PAHO / WHO BioCubaFarma National research centers: Finlay Vaccine Institute (IFV); Center of Genetic Engineering and Biotechnology (CIGB); Center of Molecular Immunology (CIM); Center for Control of Drugs, Equipment and Medical Devices (CECMED); National Center for Animal and Plant Health (CENSA); Tropical Medicine Institute "Pedro Kourí" (IPK); National Center for Biopreparations (BioCEN); Center for Drug Research and Development (CIDEM); Center for Clinical Trials (CENCEC); among others International Manufacturers and Companies The key objectives of the Congress are: To provide a progressive state-of-the-art report for scientists, manufacturers, governmental authorities and healthcare workers, who need to be updated about the latest scientific developments for human vaccines, including basic science, product development, market introduction, immunization programs and epidemiological surveillance. To promote the scientific collaboration among experts and institutions through the experience exchange, the presentation of results and the discussion on the conference topics. To accelerate progress in the development of vaccines and the acceptance and introduction of new methods and technologies. Opening lectures, oral presentations and posters will provide you the opportunity to be involved in a high quality congress to discuss about the progress in the field of immunology and pharmacology sciences(AU)

Effect of Three Chinese Herbs Processed with Different Proportions of Glycyrrhizae Radix et Rhizoma on Pharmacokinetics of Dapsone in Rats / 中国实验方剂学杂志

Objective::To investigate the processing purpose of Morindae Officinalis Radix (MO), Euodiae Fructus (EF) and Polygalae Radix (PR) processed by Glycyrrhizae Radix et Rhizoma (Gly). Method::The content of dapsone in rat plasma was determined by high performance liquid chromatography (HPLC), the mobile phase was acetonitrile (A)-water (B) for gradient elution (0-5 min, 10%-25%A; 5-20 min, 25%A) and detection wavelength was set at 292 nm. PK Solution 2.0 software was used to simulate pharmacokinetic parameters. Result::Within 300 min after dapsone was administrated, compared with the control (CTL) group, the elimination of dapsone was slowed down and its plasma concentration was increased in the unprocessed product of MO (UMO) group. The elimination of dapsone was accelerated and its peak concentration (Cmax) was decreased in the processed products of MO with Gly (GMO) groups, and they had positive correlation with proportion of Gly in GMO. Compared with the CTL group, the elimination of dapsone was slowed down, and its plasma concentration was increased and its peak time (Tmax) was postponed in the unprocessed product of EF (UEF) group, while their Cmax and Tmax were changed in the processed products of EF with Gly (GEF) groups. Compared with the CTL group, the elimination of dapsone was slowed down and its plasma concentration was increased in the unprocessed product of PR (UPR) group, while the elimination was accelerated and its plasma concentration was decreased in the processed products of PR with Gly (GPR) groups. Conclusion::The elimination of dapsone is slowed down in rats administered with UMO, UEF and UPR, while its elimination is accelerated in rats administered with the processed products of these three herbs with different proportions of Gly. Among the proportions, effect of processed products of these three herbs with 100∶6 (ratio of unprocessed product-Gly) on pharmacokinetics of dapsone is not significant.

Expression and clinical significance of aryl hydrocarbon receptor in peripheral blood and skin lesions of patients with atopic dermatitis / 中华皮肤科杂志

Objective To detect levels of aryl hydrocarbon receptor (AhR) and its downstream molecules in peripheral blood mononuclear cells (PBMCs) and sera from patients with atopic dermatitis (AD),and to analyze the correlation of their expression with serum cytokines and the severity of AD.Methods Real-time quantitative PCR (RT-PCR) was performed to analyze mRNA expression of AhR,cytochrome P4501A (CYP1A1),AhR repressor (AHRR),AhR nuclear translocator (ARNT) in PBMCs from 29 AD patients and 17 healthy controls,enzyme-linked immunosorbent assay (ELISA) to detect serum levels of interleukin (IL)-1β,IL-6,tumor necrosis factor (TNF)-α,IL-4,IL-22 and AhR in the AD patients,and immunohistochemical study to determine AhR expression in skin lesions of the AD patients and normal skin tissues of 21 patients with pigmented nevus.Measurement data were compared by using unpaired Student's t test,enumeration data were compared by using chi-square test,and correlations between indices were analyzed by using Pearson correlation analysis.Results The serum level of AhR was significantly higher in the AD group (41.26 ± 4.52 pmol/L) than in the healthy control group (33.73 ± 2.49 pmol/L,t =6.507,P ＜ 0.001).Compared with the healthy control group,the AD group showed significantly increased mRNA expression ofAhR (1.572 ± 0.392 vs.1.000 ± 0.173,t =6.819,P =0.007),AHRR (2.402 ±1.716 vs.1.000 ± 0.788,t =3.722,P =0.039),CYP1A1 (2.258 ± 1.598 vs.1.000 ± 0.796,t =3.400,P =0.002) and ARNT (1.383 ± 0.842 vs.1.000 ± 0.586,t =1.653,P =0.105) in PBMCs.The AhR expression in skin lesions in the AD group was significantly higher than that in normal skin tissues in the control group (0.191 ± 0.041 vs.0.087 ± 0.017,t =10.036,P ＜ 0.001).In the AD group,the mRNA expression of AhR in PBMCs was positively correlated with eczema area and severity index score (r =0.448,P =0.019) and the serum IL-6 level (r =0.377,P =0.046),and the AHRR mRNA expression was positively correlated with the serum IL-1β level (r =0.467,P =0.021).Conclusion AhR and its downstream molecules were highly expressed in the AD patients compared with healthy controls,and the AhR expression was positively correlated with the serum IL-6 level and AD severity in AD patients,suggesting that the AhR signaling pathway may play a certain role in pathogenesis of AD and AhR may serve as an efficient index for evaluating AD severitv.

Association between cytochrome P450 gene polymorphism and drug-induced liver injury / 临床肝胆病杂志

As the prevalence rate of drug-induced liver injury increases year by year, the pathogenesis of drug-induced liver injury has become the focus of attention. As a large family, CYP450 enzymes participate in almost all oxidative metabolic reactions of drugs in the human liver. Recent studies have shown that CYP450 enzyme gene polymorphisms lead to the differences in pharmacodynamics between individuals, and therefore, exploring the role of CYP450 enzyme gene polymorphisms in drug-induced liver injury may promote the understanding of the pathogenesis of drug-induced liver injury. This article reviews the CYP450 enzyme polymorphisms that have been found to be associated with drug-induced liver injury.

In Silico Identification of Novel Tuberculosis Drug Targets in Mycobacterium tuberculosis P450 Enzymes by Interaction Study with Azole Drugs

@#Introduction: Tuberculosis (TB) is one of the utmost serious infectious diseases worldwide. The emergence of multidrug resistance demands the development of better or new putative drug targets for tuberculosis. Recent studies suggest Mycobacterium tuberculosis cytochrome P450 enzymes as promising drug targets and azole drugs as potential inhibitors. Methods: Various computational tools, like Expasy Protparam, Swiss model, RaptorX and Phyre2 were used to analyze 12 Mycobacterium tuberculosis P450 enzymes and determine their three-dimensional structure. The structural validation was done through a Ramachandran plot using RAMPAGE server. The docking of P450 enzymes with azole drugs was done with autodock ver 4.2.6. Results: Based on sub-cellular localization prediction using CELLO tool, P450 enzymes CYP123A1, CYP132A1, CYP135A1, CYP136A1, CYP140A1, and CYP143A1 were predicted to be in the cytoplasm. Through structure assessment by Ramachandran plot, the best homology modelled proteins were docked with azole drugs like clotrimazole, croconazole, econazole, fluconazole, itraconazole, itraconazole, ketaconazole and micronazole by using autodock. By docking method it is identified that ketaconazole drug has a high affinity towards most of the mycobacterium P450 enzymes followed by the itrconazole drug. CYP123A1 enzyme is preferable as a drug target due to high binding affinity towards ketoconazole followed by CYP135A1, CYP140A1 enzymes. Conclusion: This study would help in identifying putative novel drug targets in Mycobacterium tuberculosis, which can lead to promising candidates for the optimization and development of novel anti-mycobacterial agents.

Gender differences in cytochrome P450 enzyme and UDP-glucuronosyltransferase mediated metabolic stabilities of bakuchiol in rat and human liver microsomes / 中国药理学与毒理学杂志

OBJECTIVE: To investigate the metabolic characteristics of bakuchiol mediated by cytochrome P450 enzyme (CYP) and UDP-glucuronosyltransferase (UGT) in rat liver microsomes (RLMs) or human liver microsomes (HLMs), and to compare the metabolic gender differences. METHODS: Bakuchiol was incubated at 37? with male and female RLMs or HLMs in the presence of nicotinamide adenine dinucleotide phosphate (NADPH) or uridine 5′-diphosphoglucuronic acid (UDPGA). The residual concentrations of bakuchiol were measured in each incubation system using high performance liquid chromatography (HPLC). The metabolic stability and metabolic gender differences of bakuchiol were evaluated by the remaining percentage of bakuchiol after incubation.RESULTS: When bakuchiol was metabolized by CYP in RLMs, the intrinsic clearance (Clint) value in male RLMs ?(326.6±15.4) mL·min-1·kg-1?was significantly higher than that of female RLMs ?(77.2±4.8) mL·min-1·kg-1? (P<0.01). When bakuchiol was metabolized by UGT in RLMs, female RLMs had a significantly higher Clint value ?(419.1±24.1) mL·min-1·kg-1? than male RLMs ?(164.5±8.4) mL·min-1·kg-1? (P<0.01). When bakuchiol was metabolized by both CYP and UGT in RLMs, male RLMs had a significantly higher Clint value ?(1063.1±27.2) mL·min-1·kg-1? than female RLMs ?(781.2±16.5) mL·min-1·kg-1?(P<0.01). When bakuchiol was metabolized by CYP in HLMs, male HLMs had a significantly higher Clint value ?(24.8±2.1) mL·min-1·kg-1? than female HLMs ?(17.6±1.0) mL·min-1·kg-1? (P<0.01). There were no significant gender differences in the metabolism of bakuchiol when it was metabolized by UGT in HLMs. The Clint values were 176.4±26.5 and (165.9±8.6) mL·min-1·kg-1, respectively. The metabolic parameters of bakuchiol mediated by CYP and UGT in HLMs had no significant gender differences. The Clint values were 262.5±20.9 and (236.2±10.5) mL·min-1·kg-1, respectively. CONCLUSION Bakuchiol can be metabolized by CYP and UGT in RLMs or HLMs, and the metabolic parameters exhibit species differences and gender differences.

Association study between a genetic polymorphism in cytochrome P450 19 gene rs10046 and colon and rectal cancer / 中国医师杂志

Objective To investigate the relationship between the polymorphism of cytochrome P450 19 (CYP19) gene rs10046 and the risk of colon and rectal cancer.Methods Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze gene polymorphism in CYP 19 gene rs10046 in 198 cases of colon and rectal cancer patients (case group) and 309 cases of healthy controls (control group).The genotype frequency and relative risk of CYP19 gene rs10046 between the two groups were compared and the relationship with the clinicopathological features of colorectal cancer was analyzed.Results In case group,the prevalence rates of CYP19 rs10046 genotypes C/C,C/T and T/T were 28.3％,44.4％ and 27.3％,respectively,and 17.2％,51.8％ and 31.1％ in the control group,respectively,with statistical significant difference (P ＜ 0.05).Compared with wild-type C/C,the susceptibility of colorectal cancer with the genotypes of C/T and T/T was decreased by 0.521 (95％ CI:0.330-0.822)and 0.532 (95 ％ CI:0.322-0.880) respectively.Moveover,in the non-smoking group,the risk of colorectal cancer with genotype T/T or C/T was decreased by 0.409 (95％ CI:0.210-0.798) compared with genotype C/C.The interaction was not exist in smoking group.Conclusions The polymorphism of CYP19 gene rs10046 is related to the susceptibility of colon and rectal cancer.The T/T,C/T genotype of CYP19 rs10046 decrease the risk of colon and rectal cancer,and which might be the protective factor of colon and rectal cancer.

Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase gene mutation: a case report / 中华围产医学杂志

We hereby reported the clinical manifestations and genetic diagnosis of a rare case of congenital adrenal hyperplasia (CAH) caused by cytochrome P450 oxidoreductase ( POR ) gene mutation. The case was an 11-year-old girl presented with craniofacial and skeletal malformation such as a depressed nasal bridge, radiohumeral synostosis and camptodactyly in feet. Moreover, she was diagnosed with ambiguous genitalia, and her mother had obvious masculine features during pregnancy. Laboratory tests showed that the levels of peripheral blood progesterone, 17-hydroxyprogesterone and adrenocorticotrophic hormone (ACTH) had increased significantly, which were consistent with the symptom of CAH. Genetic testing revealed a complex heterozygous mutation in POR gene of maternally inherited c.744C>G (p.Tyr248Ter) and paternal inherited c.1370G>A (p.Arg457His). Therefore, she was diagnosed with cytochrome P450 oxidoreductase deficiency (PORD), which is a rare type of CAH. The patient received oral glucocorticoid therapy and underwent knee arthroplasty.

Effect of cytochrome P450 2C19 genotypic polymorphism on treatment efficacy for gastroesophageal reflux disease by rabeprazole / 中国基层医药

Objective To investigate whether the effect of rabeprazole in treating gastroesophageal reflux disease is related to CYP2C19 gene polymorphisms.Methods 278 patients with gastroesophageal reflux disease confirmed by endoscopy and proton-pump inhibitor testing were enrolled in this study,including non erosive reflux disease (NERD) in 122 cases,the reflux esophagitis (RE) in 98 cases and Barrett esophagus in 58 cases.They were treated with rabeprazole for 8 weeks.GerdQ scores before and after the treatment were completed,endoscopy was performed again in patients with RE after treatment.The blood CYP2C19 genotyping was detected by matrix assisted laser desorption ionization time of flight mass spectrum(MALDI-TOF-MS).Results According to the genotype of CYP2C19,they were divided into extensive metabolizers,intermediate metabolizers and poor metabolizers,accounted for 39.57%,42.45% and 17.98%,respectively.There was no significant difference in GerdQ scores of three groups before treatment,and also had no significant difference after 8 weeks treatment,but in each subgroup GerdQ scores after treatment was decreased significantly than before treatment.The total effective rate of 98 patients with RE by endoscopy was 86.73%,but there was no significant difference in total effective rate of the three groups after treatment.Conclusion Rabeprazole is effective in the treatment of gastroesophageal reflux disease.Moreover,rabeprazole is less affected by CYP2C19 genotype and therefore its curative effect is more stable.

Effect of CYP2C9 gene polymorphism on warfarin dosage / 中华老年心脑血管病杂志

Objective To study the association between CYP2C9 gene polymorphism and warfarin maintenance dosage in anticoagulation therapy.Methods 200 Han patients admitted to our hospital for heart valve replacement were included in this study.CYP2C9 * 2,CYP2C9 * 3,CYP2C9 *c65 in CYP2C9 gene were sequenced using the CAPS technique and conventional DNA sequencing method.Dosages of warfarin used in patients carrying different genes were analyzed.Results No mutation of CYP2C9 * 2 but only one kind of allele C was detected in 200 patients.The genotype of CYP2C9 * 2 was C/C wild type.Allelic gene was detected at CYP2C9 * 3 A and C,with A/A wild type detected in 171 patients,A/C heterozygote mutation type detected in 18 patients,and C/C heterozygote mutation type detected in 11 patients respectively.The frequency of allelic genes A and B was 94.3 ％ and 5.7 ％ respectively.A significant difference was found between CYP2C9 * 3 mutation and warfarin dosage (P＜0.05).The dosage of warfarin reduced 18.46％ and 76.0％ respectively in patients carrying A/C heterozygote mutation type and in those carrying C/C heterozygote mutation type.Two kinds of allelic gene were detected at CYP2C9 * c65 G and C,with G/G wild type detected in 182 patients and G/C heterozygote mutation type detected in 18 patients respectively.No significant association was found in warfarin maintenance dosage for patients carrying G/G wild type and G/C heterozygote mutation type.Conclusion CYP2C9 gene polymorphism is associated with warfarin maintenance dosage in anticoagulation therapy.

Correlation between cytochrome P450 2C19 gene polymorphism and cardiovascular event after PCI in coronary heart disease / 重庆医学

Objective To investigate the correlation between cytochrome P450(CYP) 2C19 gene polymorphism with major adverse cardiovascular events(MACE) after PCI in the patients with coronary heart disease(CHD).Methods A total of 233 patients with CHD undergoing PCI in the cardiology department of our hospital from January 2014 to January 2015 were selected.All patients were given the standardized dual anti-platelet therapy of aspirin and clopidogrel.The occurrence situation of MACE within 1 year(unstable angina pectoris,cardiac death,in-stent restenosis,non-fatal myocardial infarction) was obtained by follow up.All patients were divided into the MACE group and non-MACE group.The PCR solubility curve was adopted to detect the CYP2C19 gene polymorphism.Results Among 233 cases of CHD,37 cases (15.88％) developed cardiovascular events and 196 cases (84.12 ％) did not develop vascular events;the age,sex,hypertension and diabetes mellitus had no statistical differences between the two groups(P＞0.05).The frequency of CYP2C19 * 1 in the included cases was 68.45％,which of CYP2C19 * 2 was 28.33％ and which of CYP2C19 * 3 was 3.22％.The extensive-metabolism,intermediate metabolism and slow metabolism types in the cardiovascular events group accounted for 5.41 ％,64.86 ％ and 29.73 ％ respectively,while which in the non event group were 59.69 ％,29.08％ and 11.22％ respectively,the CYP2C19 genotype distribution had statistically significant difference between the two groups(P＜0.05).The multivariate Logistic regression analysis showed that CYP2C19 intermediate metabolism type [OR 2.562,95％CI(2.825,7.350),P=0.021 0],slow metabolism type [OR 5.139,95％CI(1.289,5.232),P＜0.01],hypertension [OR 2.480,95 ％CI(1.079,5.698),P=0.032 4],smoking[OR 4.802,95％CI(1.082,18.371),P=0.029 0] were the independent risk factors for the occurrence of cardiovascular events in the patients with CHD.Conclusion CYP2C19 * 2 and CYP2C19 * 3 gene polymorphism are the independent risk factors for MACE occurrence after PCI in the patients with CHD.