Effect of cytochrome P4502C19(CYP2C19)gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI

Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronary intervention(PCI).Methods In total,675 patients were enrolled.Based on the platelet inhibition rate,patients were categorized into two groups:clopidogrel low responsiveness(CLR)and normal clopidogrel responsiveness(NCR).The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment.Patients were classified into three groups(normal metabolizer,intermediate metabolizer,and poor metabolizer)based on the CYP2C19 genotype.We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity.The cumulative rates of 12-month all-cause deaths,major adverse cardiovascular events(MACCEs),and bleeding events were calculated.Results CLR was observed in 44.4%of the overall population.Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes(P<0.05).At the 12-month follow-up,13 patients(1.9%)died and 96 patients(14.2%)experienced MACCEs.Patients with CLR(9.6%vs.11.7%vs.22.1%,P<0.05)or poor metabolizer(10.7%vs.16.4%vs.22.6%,P=0.026)experienced a higher rate of MACCEs.A MACCEs risk score between zero and two was calculated.The highest incidence of MACCEs significantly increased with the 2-positive results,and the area under the curve(AUC)was 0.712(95%CI:0.650-0.774,P<0.05).There was no significant difference between the group with a score of one and the occurrence of MACCEs(P>0.05).Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism.CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI,which is better than either test alone.

Relationship between the acid-suppression efficacy of proton pump inhibitors and CYP2C19 genetic polymorphism in patients with peptic ulcer

Objective To investigate acid-suppression efficacy of proton pump inhibitors(PPIs) in relation to CYP2C19 genetic polymorphism on patients with peptic ulcer. Methods By an open, randomized and control trial, fifty nine patients with active peptic ulcer were randomly assigned to receive one of three PPIs on a single dose (20 mg of each drug): omeprazole group (n=19), rabeprazole group (n=20) and esomeprazole group (n=20). Intragastric pH was recorded 1 hour before and 24 hours after administration. CYP2C19 genotype was tested in all patients. Results The EMs/PMs ratio of each group was 16/3,17/3 and 17/3, respectively. The total time that intragastric pH>4, time percent pH>4 and median pH in PMs patients were significantly higher than those in EMs patients of omeprazole group (P<0.05). But all these differences were not found in rabeprazole group and esomeprazole group. The pH of nocturnal acid breakthrough(NAB) in both rabeprazole group and esomeprazole group was higher than that of omeprazole group, while there was no significant difference between rabeprazole group and esomeprazole group.Conclusion The acid-suppression efficacy of omeprazole is highly dependent on CYP2C19 genetic polymorphism, while CYP2C19 genetic polymorphism may have a little influence on the acid-suppression efficacy of rabeprazole and esomeprazole. The acid-suppression action of rabeprazole and esomeprazole is superior to omeprazole, especially on night acid secretion.

CYP CYP2C1919基因检测在氯吡格雷个体化用药中的应用价值

目的探讨CYP2C19基因检测在氯吡格雷个体化用药中的应用价值。方法选取医院2023年5月至10月收治的冠状动脉介入术(PCI)后使用氯吡格雷的患者90例,根据CYP2C19基因检测结果指导患者用药,比较不同基因型患者心脏管疾病不良反应发生率。结果慢代谢型心力衰竭、心律失常、冠状动脉粥样硬化性心脏病及脑出血发生率显著高于其他类型(P<0.05);而中间代谢型心脑血管疾病发生率显著高于快代谢基因型(P<0.05);CYP2C19基因不同分型下药物皮疹结肠炎、胃肠道出血及粒细胞缺乏发生率无显著差异(P>0.05)。结论CYP2C19基因检测可评估患者机体药物代谢情况,可用于调整氯吡格雷的用药方案。

高原世居藏族和移居汉族人群 CYP2C19 基因多态性比较分析

目的比较细胞色素P450(cytochrome P450,CYP450)的同工酶CYP2C19在高原世居藏族和移居汉族人群中的不同基因型及等位基因分布特点,为高原地区抗血小板药物氯吡格雷使用前是否进行基因检测提供依据。方法选取2021年1月至12月在西藏自治区人民医院就诊的藏、汉人群(分别为200例、120例),采用荧光定量PCR检测藏、汉人群CYP2C19基因多态性,并比较高原地区藏、汉人群基因型和代谢型的分布特点。结果CYP2C19在高原地区藏、汉人群中*1/*1、*1/*2、*1/*3、*2/*2、*2/*3、*3/*3基因型分布频率分别为49%、36.5%、6.5%、7.5%、0.5%、0%和47.5%、39%、4%、6%、2.5%、1%,等位基因*1、*2、*3分布频率分别为70.5%、26%、3.5%和69.1%、26.7%、4.2%,两组间基因型和等位基因分布差异无统计学意义(P>0.05);快代谢(EM,*1/*1)、中间代谢(IM,*1/*2、*1/*3)、慢代谢(PM,*2/*2、*2/*3、*3/*3)分布频率分别为49%、43%、8%和47.5%、42.5%、10%,两组间差异亦无统计学意义(P>0.05)。结论高原世居藏族人群中CYP2C19基因代谢型和基因型与移居汉族人群比较无差异,且中间代谢型及慢代谢型人群占比超过50%。在高原地区藏、汉人群中使用氯吡格雷之前有必要进行CYP2C19基因型检测,并根据基因型结果调整用药。

Relation of cytochrome P450 2C19 gene 681G>A single nucleotide polynmrphism to clopidogrel resistance after PCI in Chinese

Objectives Clopidogrel is a prodrug that has to be converted to an active metabolite by hepatic cytochrome P450(CYP) isoenzymes to inhibit platelet aggregation.Individualvariability of platelet inhibition by clopidogrel suggests a possibility for genetic factors having a significant influence on clopidogrel responsiveness.In this study,we sought to determine the association between the single nucleotide polymorphism of CYP 2C19 681G】A and the occurrence of clopidogrel resistance(CR) in Chinese.Methods The study enrolled 614 hospitalized patients who underwentsuccessful percutaneouscoronary intervention with drug-eluting stents were received the treatmentwith dual antiplatelet regimen(aspirin plus clopidogrel).All patients received loading doses of 600 mg clopidogrel and 300 mg aspirin.20μmol/L ADP-induced platelet aggregation ratio(PAR ) was assessed 24 h after clopi- dogrel administration.The maximum residual PAR≥70%was defined as CR.Genomic DNA was extracted from whole blood samples according to standard protocols,the single nucleotide polymorphism of the CYP2C19 681G】A was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all the patients.Results CR was found in 126 patients(20.5%).There was CYP2C19 681G】A polymorphism in the study population.The frequencies of the three kinds of genotypes(GG,GA,A A) in CR group and non-CR (NCR)group were 32.5%,47.6%,19.8%and 48.0%, 45.0%,7.0%,respectively.The frequency of AA genotype was significantly higher in NCR group than that in CR group (OR =3.03,95%CI:1.889～5.784,P=0.003).The A allele carriers were more likely to develop clopidogrel resistance compared with that of G allele carriers(OR=1.85,95%CI: 1.392～2.459,P=0.002).Conclusions CYP2C19 681G/A polymorphism is associated with the risk of CR,and the A allele carriers may be a possible genetic susceptibility factor for patients with CR.

丙戊酸药物浓度与 CYP2C19 基因多态性关系的研究

目的:寻找丙戊酸药物浓度与CYP2C19基因多态性的关系,以便临床根据患者的基因型进行个体化给药。方法:运用血药浓度监测仪测定患者血药浓度和变性高效液相色谱法检测癫痫患者的CYP2C19基因多态性位点,对二者结果进行相关性分析。结果:51名汉族癫痫患者中有29名携带突变型CYP2C19基因,其中19名(65.52％)患者丙戊酸实际血药浓度较预期的血药浓度升高,血药浓度分布曲线右移。结论:CYP2C19参与丙戊酸的代谢。对于含突变型CYP2C19基因的患者应给予小剂量丙戊酸,以减少药物不良反应的发生和药物资源的浪费。

武汉地区冠心病患者氯吡格雷药物代谢相关基因 CYP2C19的多态性分布分析

目的：探讨武汉地区冠心病介入患者氯吡格雷代谢相关基因 CYP2C19多态性的分布。方法选取2014年1月-12月武汉大学人民医院心内科进行介入治疗（PCI）的316例冠心病患者作为研究对象。通过基因芯片法检测氯吡格雷代谢相关的 CYP2C19＊1，＊2，＊3基因，并将患者按 CYP2C19基因型别分为不同代谢类型：强代谢型（＊1／＊1），中间代谢型（＊1／＊2，＊1／＊3），弱代谢型（＊2／＊2，＊3／＊3，＊2／＊3）。结果根据 CYP2C19基因多态性位点功能代谢分型，携带 CYP2C19＊1的强代谢型（＊1／＊1）占43.4％，携带 CYP2C19＊2或＊3的中间代谢型（＊1／＊2和＊1／＊3）及弱代谢型（＊2／＊2，＊2／＊3和＊3／＊3）分别占42.4％，14.2％。不同性别在 CYP2C19基因分型上差异无统计学意义。结论武汉地区冠心病介入患者中分布有较多的 CYP2C19氯吡格雷代谢功能缺失基因。

CYP2D6 CYP2C19*2基因多态性与利培酮治疗精神分裂症临床效应的相关研究

目的探讨CYP2D6和CYP2C19基因多态性与利培酮治疗精神分裂症临床效应个体差异之间的相关性。方法应用聚合酶链反应(PCR)与DNA测序相结合的方法检测精神分裂症患者CYP2D6和CYP2C19基因多态性。应用高效液相色谱分别测定利培酮、9-羟利培酮的血药浓度,以治疗前后阳性和阴性症状量表(PANSS)评分减分率评价药物临床疗效,比较不同基因型之间血药浓度和药物临床疗效的差异。结果55例单用利培酮治疗的精神分裂症患者,CYP2D6(C100T)不同基因型之间利培酮血药浓度分布差异有统计学意义(P<0.05),但该位点与该药的临床效应之间没有相关性(P>0.05)。CYP2C19*2(G681A)基因多态性与利培酮在体内代谢以及该药临床效应之间差异无统计学意义(P>0.05)。结论CYP2D6(C100T)对利培酮血药浓度有影响,但与利培酮的临床效应个体差异间无相关性。CYP2C19*2(G681A)可能不是引起利培酮代谢以及临床效应个体差异的主要因素。

Time serial transcriptome reveals Cyp2c29 as a key gene in hepatocellular carcinoma development

Objective:Hepatocellular carcinoma(HCC)is a severely lethal cancer that usually originates from chronic liver injury and inflammation.Although progress on diagnosis and treatment is obvious,the cause of HCC remains unclear.In this study,we sought to determine key genes in HCC development.Methods:To identify key regulators during HCC progression,we performed transcriptome sequencing to obtain time series gene expression data from a mouse model with diethylnitrosamine-induced liver tumors and further verified gene expression and function in vitro and in vivo.Results:Among the differentially expressed genes,Cyp2c29 was continuously downregulated during HCC progression.Overexpression of Cyp2c29 suppressed N F-kB activation and proinflammatory cytokine production by increasing the production o f 14,15-epoxyeicosatrienoic acid in vitro.Furthermore,overexpression of Cyp2c29 in vivo protected against liver inflammation in mouse models of liver injury induced by both acetaminophen and CC14.Two human homologs of mouse Cyp2c29,CYP2C8 and CYP2C9,were found to be downregulated in human HCC progression,and their expression was positively correlated with overall survival in patients with HCC(significance:P=0.046 and 0.0097,respectively).Conclusions:Collectively,through systematic analysis and verification,we determined that C yp2c29 is a novel gene involved in liver injury and inflammation,which may be a potential biomarker for HCC prevention and prognosis determination.

Genetic Polymorphisms of CYP2C9: Comparison of Prevalence in the Lebanese Population with Other Populations

Background: There is little knowledge about genotyping of cytochrome P450s in the Middle East, and there has not been any report on the genotype of CYP 2C9 allelic variants in Lebanese population. Aims and objectives: The purpose of the study was to determine and compare the frequencies of the cytochrome P450 CYP2C9 variants in the Lebanese population with the frequencies in other ethnic populations. Methods: CYP2C9 genotypes were determined in a total of 146 samples of unrelated, healthy Lebanese individuals residing in different areas in Lebanon. Following DNA extraction from buccal cells and polymerase chain reaction, genotyping was performed by Pyrosequencing method. CYP2C9 genotypes results were compared to other populations;i.e., Middle Easterns, Europeans, Asians, and African Americans. Results and discussion: The frequencies of the CYP2C29*2, CYP2C9*3, and CYP2C9*4 alleles were 11.305%, 11.645%, and 1.025% respectively. No CYP2C9*5 allele variants were found among the Lebanese study sample. Vol- unteers could be divided into three CYP2C9 genotype groups: subjects (76.71%) with no mutated alleles (CYP 2C9*1*1;homozygous extensive metabolizers, EM), 21.23% with one mutated allele (CYP 2C9*1*2, *1*3, *1*4, and *1*5;heterozygous intermediate metabolizers IM), and 2.06% with two mutated alleles, homozygous variants as poor metabolizers, PM). The comparative analysis using genotype groups of different populations showed differences among Leba- nese and other Caucasians. Conclusion: This is the first report from Lebanon on CYP2C9 variants;it highlights a higher frequency of CYP2C9 extensive metabolizers compared to other populations including Caucasians. The results serve as a database on CYP 2C9 polymorphisms and baseline clinical data for dosing and avoiding adverse drug reac- tions of drugs metabolised by CYP2C9 in Lebanese patients.

CYP2C19＊2, CYP2C19＊3, CYP2C19＊17 Allele and Genotype Frequencies in Clopidogrel-Treated Patients with Coronary Heart Disease in Russian

Individual variation in the response to drug therapy has been mainly attributed to the genetic polymorphism of cytochrome P 450 isoenzymes. Mutation in the gene CYP2C19 （cytochrome P450 2C19） has been shown to influence the clinical efficiency of clopidogrel. The aim is to investigate the frequencies of CYP2C19＊2 （c.G681A; rs4244285）, CYP2C19＊3 （c.G636A; rs4986893）, CYP2C19＊17 （c.C806T; rs12248560） and to compare the allele and genotype frequencies of CYP2C19＊2 in patients with CHD （coronary heart disease） to healthy volunteers. We examined 53 patients with CHD received clopidogrel and 146 healthy volunteers. CYP2C19＊2, CYP2C19＊3, CYP2C19＊17 carriages were determined by a polymerase-chain reaction. The observed genotype distribution did not deviate from Hardy-Weinberg equilibrium, it was determined by a Chi-square test with Yates correction. The frequency of CYP2C19＂2 allele reported in patients with CHD and in the healthy volunteers was 16.6% and 13.3%, respectively （P = 0.584）. The results of the present study may be helpful in developing current and future directions for its management.

First-line eradication for Helicobacter pylori-positive gastritis by esomeprazole-based triple therapy is influenced by CYP2C19 genotype

AIM: To evaluate the effect of first line esomeprazole(EPZ)-based triple therapy on Helicobacter pylori(H. pylori) eradication.METHODS: A total of 80 Japanese patients with gastritis who were diagnosed as positive for H. pylori infection by endoscopic biopsy-based or ^(13)C-urea breath tests were included in this study. The average age of the patients was 57.2 years(male/female, 42/38). These patients were treated by first-line eradication therapy with EPZ 40 mg/d, amoxicillin 1500 mg/d, and clarithromycin 400 mg/d for 7 d. All drugs were given twice per day. Correlations between H. pylori eradication, CYP2C19 genotype, and serum pepsinogen(PG) level were analyzed. This study was registered with the UMIN Clinical Trials Registry(UMIN000009642).RESULTS: The H. pylori eradication rates by EPZbased triple therapy evaluated by intention-to-treat and per protocol were 67.5% and 68.4%, respectively, which were similar to triple therapies with other first-generation proton pump inhibitors(PPIs). The eradication rates in three different CYP2C19 genotypes, described as extensive metabolizer(EM), intermediate metabolizer, and poor metabolizer, were 52.2%, 72.1%, and 84.6%, respectively. The H. pylori eradication rate was significantly lower in EM than non-EM(P < 0.05). The serum PG?Ⅰ?level and PG?Ⅰ/Ⅱ ratio were significantly increased after eradication of H. pylori(P < 0.01), suggesting that gastric atrophy was improved by H. pylori eradication. Thus, first-line eradication by EPZbased triple therapy for patients with H. pylori-positive gastritis was influenced by CYP2C19 genotype, and the eradication rate was on the same level with other firstgeneration PPIs in the Japanese population.CONCLUSION: The results from this study suggest that there is no advantage to EPZ-based triple therapy on H. pylori eradication compared to other firstgeneration PPIs.

Association of CYP2C19 genotype with type 2 diabetes

Background: CYP2C19 is a major isoform of cytochrome P450 that metabolizes a number of commonly prescribed drugs such as omeprazole, diazepam, tolbutamide and propranolol. Its expression is regulated by the constitutive androstane receptor (CAR), involved in glucocorticoids synthesis. Since a number of crossliniks have been described for CYPs and some hormones, an association of CYP2C19 with type 2 diabetes is likely. Methods: Two groups were studied, 352 diagnosed with type 2 diabetes patients and 342 healthy volunteers form Mexico City. Both groups were tested for CYP2C19*2 and *3 alleles. We carried out an allelic discrimination using TaqMan assay for *2, and used FRET sensor and anchor probes for *3. Results: Ninety one percent of the subjects had the wild type allele, 9% have the *2 allele;no subject presented the *3 allele. The CYP2C19*2 allele is associated with type 2 diabetes (p = 0.012). Admixmap program was used to correct the admixture of this population and get the correlation. This was further confirmed in a linear model with a 67% power and by the method of Strom and Wienker for association on subjects within the mean range of Amerindian ancestry only (60%). Conclusion: Type 2 diabetes patients have significatly more *2 allele than healthy volunteers, more evident for the patients with the homocygous genotype.

Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA

Conclusions:Among Chinese patients with minor ischemic stroke or TIA who were carriers of CYP2C19 loss-of-function alleles,the risk of stroke at 90 days was modestly lower with ticagrelor than with clopidogrel.The risk of severe or moderate bleeding did not differ between the two treatment groups,but ticagrelor was associated with more total bleeding events than clopidogrel.(Funded by the Ministry of Science and Technology of the People's Republic of China and others;CHANCE-2 ClinicalTrials.gov number,NCT04078737.).

Influence of the Meal and Genotype of CYP2C19 on the Pharmacokinetics of Proton Pump Inhibitors in Healthy Japanese Subjects

Objectives: To evaluate the influence of meals on the pharmacokinetics of omeprazole and rabeprazole and to investigate these PPIs with reference to CYP2C19 genotypes in healthy Japanese men. Methods: This was a randomized, open label, four-way crossover study. Twelve healthy Japanese male volunteers received a single oral dose of either 20 mg omeprazole or 10 mg rabeprazole, in the fasted state and after a standardized breakfast. Results: Between the administration of omeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC, Tmax, and half-life. Between the administration of rabeprazole in the fasted state and after breakfast, there were no significant differences in Cmax, AUC and half-life, whereas the Tmax of rabeprazole after breakfast was significantly delayed (2.8 ± 1.0 vs 5.3 ± 1.8 h, respectively;p = 0.006). PMs demonstrated the highest Cmax and AUC after drug intake under the fasting state and after breakfast, and homo EMs showed a significantly delayed Tmax. Conclusion: When a single dose of either PPI was administered, the pharmacokinetics of omeprazole was not affected by the meal, whereas the Tmax of rabeprazole after the meal was significantly delayed.

双倍剂量氯吡格雷治疗氯吡格雷抵抗ACS患者的临床效果及 CYP2C19 酶基因型的影响

目的 探讨双倍剂量氯吡格雷治疗氯吡格雷抵抗的急性冠状动脉 综合征(ACS)的临床效果。方法 选取 2017 年 1 月至 2019 年 3 月在我院 经皮冠状动脉介入(PCI)术后的 ACS 患者 140 例,经血栓弹力图(TEG) 检查存在氯吡格雷抵抗,根据治疗方案分为观察组(n=68)和对照组 (n=72),观察组给予双倍剂量氯吡格雷治疗,对照组给予常规剂量氯吡 格雷治疗,观察两组治疗前后血小板抑制率、主要不良心血管事件(MACE)。 结果 观察组治疗后 1 周、1 个月血小板抑制率分别为(37.60±2.88)% 和(38.89±2.90)%, 明 显 高 于 对 照 组(p < 0.05);观 察 组 携 带 CYP2C19 酶功能缺失等位基因患者治疗后 1 周、1 个月血小板抑制率分别为 (30.10±2.91)% 和(31.18±3.02)%,明显低于未携带 CYP2C19 酶功能 缺失等位基因患者(p < 0.05);观察组 MACE 发生率为 7.35%,明显低 于对照组(p > 0.05);观察组携带和未携带 CYP2C19 酶功能缺失等位基 因患者 MACE 发生率差异比较无统计学意义(p > 0.05)。结论 双倍剂量 氯吡格雷治疗氯吡格雷抵抗 ACS 患者有较好的效果,但其效果受到 CYP2C19 酶基因型影响。

Impact of CYP2C19＊2 and CYP2C19＊3 Polymorphisms on the Response to Clopidogrel and Running Cost Analyses

We investigated the variability in the PFT （platelet function test） response to CYP2C19 polymorphisms and compared it with the clinical presentation. Furthermore, running cost analyses were done. One-hundred and seventy Saudi Arabian patients who were stable on 75 mg clopidogrel for ≥1 month for various cardiac indications were enrolled. We extracted DNA using the MagNA Pure LC instrument. CYP2C19 genotyping for the alleles, ＊1, ＊2 and ＊3, was conducted by real-time PCR （polymerase chain reaction）. The PFT was carried out by VerifyNow P2Y12 assay for all patients. Clinical events were documented retrospectively for all patients. One hundred and seventeen patients presented with the wild variant 1/1, 19 patients with 1/2, and 34 patients with 2/2. We could not detect ＊3. There was a significant association between different genotyping and percentage inhibitions （P = 0.0002）. 1/1 patients tended to be moderate-to-extensive metabolisers, whereas most of the other patients were slow metabolisers. The cost of doing the PFT was 250 SR （Saudi Riyals）/patient and 200 SR/patient for kits and materials （excluding equipment and labour）. The PFT varied considerably with polymorphisms, but showed no significant associations with clinical symptoms.

CYP2C19和ABCB1 C3435T基因多态性与氯吡格雷给药后ADP抑制率的关系

目的 分析CYP2C19和ABCB1 C3435T基因多态性与氯吡格雷个体化给药后二磷酸腺酐(ADP)抑制率的关系。方法 选取2017年12月—2021年1月中山大学附属第五医院神经内科和脑血管病科确诊的脑梗死或短暂性脑缺血并服用氯吡格雷抗血小板治疗的住院患者138例,所有患者均给予氯吡格雷75 mg治疗7 d后,检测患者ADP抑制率,同时利用荧光原位杂交法,检测患者CYP2C19和ABCB1 C3435T基因多态性,分析基因多态性与ADP抑制率的关系。结果 男性患者与女性患者对氯吡格雷的反应性存在显著差异(χ^(2)=6.807,P=0.033),男性患者ADP抑制率高于女性患者(t=2.686,P=0.008)。CYP2C19超快代谢型、快代谢型、中间代谢型和慢代谢型的ADP抑制率差异无统计学意义(F=1.129,P=0.340)。CYP2C19*1/*17型、*1/*1型、*1/*2型、*1/*3型、*2/*2型和*2/*3型的ADP抑制率有逐步下降的趋势,但差异无统计学意义(F=1.756,P=0.126),组间两两比较显示,*1/*1型的ADP抑制率高于*2/*2型(t=2.257,P=0.036)。ABCB1 C3435T的CC型、CT型和TT型的ADP抑制率比较差异无统计学意义(F=0.555,P=0.576)。CYP2C19快代谢型、中间代谢型和慢代谢型中ABCB1 C3435T不同基因型(CC型、CT型和TT型)的ADP抑制率比较差异均无统计学意义(F/P=0.192/0.826、0.525/0.594、0.666/0.540)。男性患者与女性患者在CYP2C19各代谢型中的分布无显著差异(U=2 146.50,P=0.608)。结论 在氯吡格雷个体化治疗中,CYP2C19基因多态性与ADP抑制率存在一定的相关性,ABCB1 C3435T基因多态性与ADP抑制率无相关性。

癫痫患者CYP2C19基因多态性与丙戊酸钠血药浓度、疗效的相关性研究

目的研究癫痫患者CYP2C19基因多态性与丙戊酸钠血药浓度、疗效的相关性。方法选取2022年8月至2023年7月乌鲁木齐市第四人民医院收治的115例癫痫患者作为研究对象,采用实时荧光聚合酶链反应(PCR)技术检测所有患者的CYP2C19基因型,同时给予丙戊酸钠治疗,将患者按CYP2C19基因型别分为强代谢型(*1/*1)47例、中间代谢型(*1/*2,*1/*3)50例和弱代谢型(*2/*2,*3/*3,*2/*3)18例,比较CYP2C19代谢型对血药浓度的影响;并根据丙戊酸钠治疗效果分为疗效良好组(n=85)和疗效不佳组(n=30),比较两组患者的一般资料,采用Logistic多因素回归分析影响丙戊酸钠治疗效果的因素。结果癫痫患者CYP2C19基因分型分布频率符合Hardy-Weinberg平衡定律检验;CYP2C19弱代谢型的丙戊酸钠血药浓度为(3.80±1.02)μg/mL,明显高于强代谢的(2.67±0.34)μg/mL和中间代谢型的(2.73±0.36)μg/mL,差异均有统计学意义(P<0.05),而强代谢型和中间代谢型的丙戊酸钠血药浓度比较差异无统计学意义(P>0.05);经单因素分析结果显示,月发病频率≥4次、继发性病因为热性惊厥、丙戊酸钠血药浓度<50μg/mL、服药依从性差、CYP2C19基因型为弱代谢型与丙戊酸钠治疗效果有关(P<0.05);经Logistic多因素回归分析结果显示,月发病频率≥4次、继发性病因为热性惊厥、丙戊酸钠血药浓度<50μg/mL、服药依从性差、CYP2C19基因型为弱代谢型均为影响丙戊酸钠治疗效果的独立危险因素(P<0.05)。结论癫痫患者的CYP2C19基因具有多态性,且与丙戊酸钠血药浓度及疗效具有相关性。因此,在采用丙戊酸钠治疗癫痫患者时,可检测CYP2C19基因分型,以指导癫痫患者的临床个体化治疗。

C反应蛋白对不同CYP2C19基因型患者伏立康唑血药浓度的影响分析

目的分析炎性指标C反应蛋白(CRP)与伏立康唑血药浓度的相关性,并进一步探究CRP对不同CYP2C19基因型患者伏立康唑血药浓度的影响。方法选取2020年3月—2023年4月使用伏立康唑静脉注射治疗侵袭性真菌感染的患者,采用LC-MS/MS法测定稳态血药浓度,采用荧光原位杂交技术检测患者CYP2C19基因多态性,同时收集患者的临床资料。根据CRP将患者分为非/轻度炎症组和中度炎症组,采用SPSS 22.0软件进行统计分析。结果共纳入122例患者,中度炎症患者伏立康唑血药浓度显著大于非/轻度炎症患者(P<0.0001);非/轻度炎症患者中,超出治疗范围上限5.0μg/ml的比例为21.05%,而中度炎症患者中该比例高达41.67%(P=0.035)。多因素线性回归分析结果显示,血小板计数、年龄、CRP及CYP2C19基因表型是伏立康唑血药浓度的独立影响因素(P<0.001)。对于快代谢及中间代谢患者,中度炎症患者的血药浓度显著大于非/轻度炎症患者(P<0.05),而慢代谢患者,CRP对伏立康唑血药浓度的影响无统计学意义(P>0.05)。结论CRP是影响伏立康唑血药浓度因素之一,且与患者CYP2C19基因表型显著相关,快代谢及中间代谢患者炎症期间使用伏立康唑应加强监测血药浓度,以避免不良反应的发生。