Therapeutic effects of 10 mg/day rabeprazole administration on reflux esophagitis was not influenced by the CYP2C19 polymorphism

BACKGROUND: The acid suppressive effects of omeprazole (OPZ) and lansoprazole (LPZ) are influenced by the CYP2C19 polymorphism. On the other hand, some investigators have reported that acid suppressive effect of rabeprazole (RPZ) was not significantly affected by CYP2C19. The present study was designed to investigate whether the CYP2C19 genotype is related to the healing of reflux esophagitis (RE) in treatment with RPZ 10 mg. METHODS: One hundred and three Japanese patients with RE were treated with daily oral administration of 10 mg RPZ. At 4 and 8 weeks after the start of treatment, healing of RE was evaluated endoscopically. The CYP2C19 genotype was investigated before the treatment. RESULTS: At 4 weeks after the start of treatment, the healing rates for homo-extensive metabolizer, hetero-extensive metabolizer, and poor metabolizer patients were 83.3% (15/18), 77.3% (17/22), and 88.9% (8/9) [corrected] respectively, and at 8 weeks after the start of treatment, the healing rates were 86.1% (31/36), 92.0% (46/50), and 82.4% (14/17), respectively. There were no significant differences in the healing rate of RE among the three genotypes at either 4 or 8 weeks after the start of treatment. CONCLUSIONS: The therapeutic effects of 10 mg/day RPZ administration on RE may be uninfluenced by the CYP2C19 polymorphism.     

CYP2C19基因多态性与PCI手术患者血小板抑制率的相关性研究

目的 研究CYP2C19基因多态性对经皮冠状动脉介入治疗（PCI）手术患者血小板抑制率的影响。方法 本研究纳入符合入选标准的2014年1月至2016年4月在解放军第一七五医院心内科住院的冠心病患者210例,均需行PCI手术治疗。所有入选者均采取静脉血标本并提取外周血基因组DNA,进行PCR 扩增及纯化,进行基因芯片杂交显色,通过生物芯片识读仪检测CYP2C19基因型,根据不同的基因型对患者进行分组。入选者服用负荷量阿司匹林+氯吡格雷24 h后采取静脉血标本,然后用血栓弹力图仪（TEG）检测并自动计算出二磷酸腺苷（ADP）诱导的血小板抑制率。结果 入选的210例患者各基因型比例分别为：（*1/*1）94例（44.8%)、（*1/*2）79例（37.6%）、（*1/*3）12例（5.7%）、（*2/*2）20例（9.5%）、（*2/*3）4例（1.9%）、（*3/*3）1例（0.5%）,其中快代谢型（EM型）94例（44.8%）、中等代谢型（IM型）91例（43.3%）、慢代谢型（PM型）25例（11.9%）,共有43例患者（20.5%）出现氯吡格雷抵抗现象（CR）。不同基因型组患者的血小板抑制率差异均有统计学意义（P<0.01）,其中PM型患者的血小板抑制率最低,IM型次之;不同基因型组患者的氯吡格雷抵抗情况差异有统计学意义（P<0.01）,其中PM型患者的CR远高于另外两组。结论 CYP2C19不同基因型对氯吡格雷抗血小板作用的影响存在显著差异,其中携带CYP2C19 *2或*3突变等位基因的PCI手术患者发生CR的风险明显增加。     

Effect of esomeprazole and rabeprazole on intragastric pH in healthy Chinese: an open, randomized crossover trial

BACKGROUND AND AIM: Esomeprazole is the S-isomer of omeprazole, with a stronger acid suppressive effect than omeprazole. This open, randomized crossover study was designed to evaluate the effect of esomeprazole and another proton-pump inhibitor, rabeprazole, on intragastric pH in healthy Chinese. METHODS: Thirty-six healthy volunteers (26 men and 10 women, aged between 20 and 31 years) were enrolled. Subjects were given either esomeprazole 40 mg (n = 18) or rabeprazole 10 mg (n = 18) orally once daily for 5 days during the first dosing period, then the other medicine at the set dosage for the second dosing period. The two periods were separated by a 14-day washout phase. The doses were chosen according to the State Food and Drug Administration of China for the treatment of acid-related diseases. Intragastric pH was continuously monitored for 24 h on days 1 and 5 of each dosing period. CYP2C19 genotypes were analyzed to identify the extensive metabolizers (EM) and poor metabolizers (PM). RESULTS: The percentage of time with intragastric pH >4 was significantly higher (P < 0.001) in subjects receiving esomeprazole than in those receiving rabeprazole in the first 4 h after administration of the first dose (70.65% vs 44.87%), at 24 h on day 1 (73.7% vs 54.8%) and at 24 h on day 5 (84.2% vs 76.2%). The median intragastric pH was also higher in subjects receiving esomeprazole than in those receiving rabeprazole in the first 6 h, day 1 and day 5 (P 4 for at least 16 h on day 1 (63.9% vs 33.3%) and on day 5 (88.9% vs 61.1%) was higher after administration of esomeprazole than after rabeprazole (both P < 0.05). On genotype analysis, 28 of the subjects were EM and eight were PM. Those who were PM tended to have a higher, albeit not statistically significant, percentage of time with intragastric pH >4 and the median 24-h intragastric pH than those who were EM. Both drugs were well tolerated. CONCLUSIONS: Esomeprazole 40 mg orally once daily is more effective and faster in increasing intragastric pH than rabeprazole 10 mg orally once daily, and thus offers a potential for improved efficacy in acid-related diseases.     

Effects of CYP2C19 and MDR1 genotype on the eradication rate of Helicobacter pylori infection by triple therapy with pantoprazole, amoxycillin and clarithromycin

Backgrounds:  CYP2C19 polymorphism plays an important role in the metabolism of proton pump inhibitors. The multidrug resistance (MDR)1 genotype is associated with the successful eradication of Helicobacter pylori . The aim of the present study was to investigate the effects of CYP2C19 and MDR1 genotypes on the eradication rate of H. pylori using a pantoprazole-based triple therapy.
Methods:  A total of 210 patients infected with H. pylori were treated with 40 mg pantoprazole, 500 mg clarithromycin and 1000 mg amoxicillin twice daily for 7 days. The CYP2C19 genotype was determined with polymerase chain reaction (PCR)–restriction fragment length polymorphism analysis. The MDR1 C3435T polymorphism was identified by PCR-based allele-specific amplification (PCR-ASA).
Results:  Of the 210 patients who completed the study, 174 (82.9%, 95.0% confidence interval [CI], 77.8–88.0%) achieved successful eradication after the first cycle of therapy. The eradication rates for H. pylori were 86.7%, 81.1% and 82.1% in the homozygous extensive, heterozygous extensive and poor metabolizer groups, respectively ( P  = 0.65). Moreover, the cure rates in the CC, CT, and TT groups were 82.7%, 84.4% and 76.9%, respectively ( P  = 0.66). Multiple logistic regression analysis revealed that endoscopic diagnosis was a significant independent risk factor for treatment failure.
Conclusion:  The eradication rates of H. pylori by pantoprazole, amoxicillin and clarithromycin were not significantly different among the CYP2C19 and MDR1 genotypes. Hence, the cure rate of H. pylori in the Korean population was no different for the CYP2C19 and MDR1 genotypes.     

CYP2C19 polymorphisms in patients with gastric and colorectal carcinoma

Background It has been reported that up to 80% of human cancer arise as a consequence of environmental exposure and host susceptibility factors. Environmental carcinogens are predominantly metabolized by the cytochrome P450 (CYP) superfamily of drug-or xenobiotic-metabolizing enzymes. Genetic variations in these enzymes affect individuals' susceptibility to carcinogens. Aim of the study The aim of this study was to evaluate the relationship between CYP2C19 polymorphism and susceptibility to these cancers by means of CYP2C19 genotyping among Turkish subjects. Methods DNA of subjects were isolated from leukocytes by high pure template preparation kit (Roche Diagnostics, GmbH, Mannheim, Germany) and genotypes were detected by LightCycler CYP2C19 Mutation Detection Kit by real-time PCR with LightCycler instrument (Roche Diagnostics, cat. no. 3113914). Results Being male was associated with a 3.5-fold (OR: 4.27, CI: 2.27–8.05) and 4.27-fold (OR: 3.50, CI: 1.948–6.301) risk for colorectal and gastric carcinoma, respectively. The CYP2C19 ^* 3 heterozygote genotype was not found in either gastric or colorectal carcinoma patients. Although the frequency of CYP2C19^*2 heterozygote genotype is high in patients with gastric and colorectal carcinoma, it is not significantly associated with cancer (OR: 1.79, CI: 0.829–3.865 and OR: 1.998, CI: 0.961–4.154, respectively). Conclusion Although the frequency of CYP2C19 ^* 2 heterozygote genotype is high in our patients with gastric and colorectal carcinoma, there is no the relationship between CYP2C19 polymorphism and susceptibility to these cancer.     

Review Article: Efficacy and safety of rabeprazole in treating gastroesophageal reflux disease

Abstract   Proton pump inhibitors (PPI) are the mainstay of gastroesophageal reflux disease (GERD) treatment. They have a good efficacy and short- and long-term safety profile. Rabeprazole is a second generation PPI with rapid onset of action that quickly relieves symptoms of GERD. Rabeprazole consistently and profoundly inhibits gastric acid secretion. Its metabolism is less dependent on CYP4502C19 system and therefore is the least affected among all PPIs by CYP4502C19 genetic polymorphism. Recent studies have also indicated that rabeprazole on-demand is cost effective in preventing non-erosive reflux disease (NERD) symptom relapse.     

CYP2C19基因多态性在消化系统中的意义

随着CYP2C19基因多态性研究的不断深入,发现它不仅存在个体差异和种群差异,而且这些差异影响酸相关性疾病及幽门螺杆菌的疗效,影响慢性肝病及肝移植患者的药物选择,影响对肿瘤高危性的判断等。此文就近年CYP2C19在消化系统中的作用作一综述。     

A study on the impact of CYP2C19 genotype and platelet reactivity assay on patients undergoing PCI

Background

A thorough understanding of the patient''s genotype and their functional response to a medication is necessary for improving event free survival. Several outcome studies support this view particularly if the patient is to be started on clopidogrel due to the prevalence of clopidogrel resistance. Such guided therapy has reduced the incidence of Major Adverse Cardiac Events (MACE) after stent implantation.

Methods

Between August 2013 and August 2014, 200 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) were prescribed any one of the anti-platelet medications such as clopidogrel, prasugrel or ticagrelor and offered testing to detect CYP2C19 gene mutations along with a platelet reactivity assay (PRA). Intended outcome was modification of anti-platelet therapy defined as either dose escalation of clopidogrel or replacement of clopidogrel with prasugrel or ticagrelor for the patients in clopidogrel arm, and replacement of ticagrelor or prasugrel with clopidogrel if those patients were non-carrier of mutant genes and also if they demonstrated bleeding tendencies in the ticagrelor and prasugrel arms.

Conclusion

Clopidogrel resistance was observed to be 16.5% in our study population. PRA was useful in monitoring the efficacy of thienopyridines. By having this test, one can be safely maintained on clopidogrel in non-carriers, or with increased dose of clopidogrel in intermediate metabolizers or with newer drugs such as ticagrelor or prasugrel in poor metabolizers. Patients on ticagrelor and prasugrel identified as non-carriers of gene mutations for clopidogrel metabolism could be offered clopidogrel resulting in economic benefits to the patients. Patients at high risk of bleeding were also identified by the PRA.     

CYP2C19基因多态性与氯吡格雷抵抗的研究现状

氯吡格雷是目前治疗急性冠状动脉综合征的一种经典抗血小板药物,能降低冠心病患者尤其是支架术后患者的主要不良心血管事件的风险。但是部分患者存在氯吡格雷抵抗。研究认为,氯吡格雷抵抗受多因素影响,CYP2C19基因多态性是最重要的内部因素。CYP2C19*2和CYP2C19*3是亚洲人群最常见类型,CYP2C19基因变异者,氯吡格雷抗血小板效应减弱,不良心血管事件增加。因此,常规检测CYP2C19基因多态性可指导临床上氯吡格雷个性化用药。     

CYP 450 2C19 polymorphisms in Indian patients with coronary artery disease

Background

Dual antiplatelet therapy is the cornerstone in the management of acute coronary syndromes (ACS) and prevention of stent thrombosis (ST). Genetic polymorphisms in CYP2C19 gene involved in hepatic activation of clopidogrel leads to clopidogrel non-responsiveness and may influence clinical outcomes. These polymorphisms in CYP2C19 gene and their impact on clinical outcome in coronary artery disease (CAD) have not been studied in Indian population.

Methods

We studied 110 consecutive patients (mean age 55.7 ± 10.7 years; 90% male) taking clopidogrel with angiographically proven CAD for various genetic polymorphisms in CYP2C19 gene. Relationship between loss of function mutation and clinical presentation with recurrent ACS including ST was analyzed.

Results

Out of 110 patients, 26 (23.64%) had normal genotype, 52 (47.23%) had loss of function mutation *2 and 39 (35.45%) had a gain of function mutation *17, 7 (6.36%) patients were undefined metabolizers (*2/*17) which were excluded from analyses. Final analyses included 103 patients, with 45 (40.90%) having loss of function. Overall 51 patients had ACS, with 27 developing recurrence while on clopidogrel. The prevalence of loss of function mutation was no different between the group with recurrences and those without recurrences (55.6% vs. 50%, p = 0.7). Two patients developed ST while on clopidogrel; both had loss of function mutation.

Conclusion

CYP2C19 gene polymorphisms are common in Indian population. Loss of function mutation status did not affect the clinical outcomes. A larger study also considering P2Y12 receptor polymorphisms together with platelet activity testing, may be required to establish the role of CYP2C19 gene polymorphisms in clinical practice.     

Review article: efficacy and safety of rabeprazole in treating gastroesophageal reflux disease

Proton pump inhibitors (PPI) are the mainstay of gastroesophageal reflux disease (GERD) treatment. They have a good efficacy and short- and long-term safety profile. Rabeprazole is a second generation PPI with rapid onset of action that quickly relieves symptoms of GERD. Rabeprazole consistently and profoundly inhibits gastric acid secretion. Its metabolism is less dependent on CYP4502C19 system and therefore is the least affected among all PPIs by CYP4502C19 genetic polymorphism. Recent studies have also indicated that rabeprazole on-demand is cost effective in preventing non-erosive reflux disease (NERD) symptom relapse.     

CYP2C19 genotype and adverse cardiovascular outcomes after stent implantation in clopidogrel-treated Asian populations: A systematic review and meta-analysis

The effect of CYP2C19 gene polymorphism on clinical outcomes of patients with coronary artery disease (CAD) treated with clopidogrel remains controversial. Ethnicity has been proposed to influence clopidogrel response following stent implantation in CAD patients with different CYP2C19 genotypes. Furthermore, Asian populations are reported to have a relatively greater prevalence of CYP2C19 loss-of-function (LOF) alleles. We aimed to evaluate the impact of CYP2C19 gene polymorphism on clinical outcomes in Asian populations who underwent percutaneous coronary interventions (PCI) and received clopidogrel therapy. We conducted a comprehensive search in PubMed, EMBASE, and Cochrane Library from their inceptions to January 20, 2017. Studies that reported clopidogrel therapy information, clinically relevant outcomes (adverse cardiovascular events, stent thrombosis and bleeding), and CYP2C19 genotypes among Asian populations were included. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death and myocardial infarction. The safety endpoint was any kind of bleeding. We retrieved 20 studies of 15056 patients reporting 1301 cardiovascular events. The primary analysis showed at least one CYP2C19 LOF allele (*2 and/or *3) carriers were at an increased risk of MACE compared with non-carriers (10.58% vs. 6.07%, OR: 1.99, 95% CI: 1.64 to 2.42, p < .001). Stent thrombosis (ST) was also more frequent in LOF allele carriers (2.22% vs. 0.44%, OR: 4.77, 95% CI: 2.84 to 8.01, p < .001). Inversely, the risk of bleeding was lower in LOF allele carriers (OR: 0.66, 95% CI: 0.46 to 0.96, p < .001). Subgroup analysis was performed to assess differences by high (600 mg) or routine (300 mg) loading dose of clopidogrel and by different nationalities. The risk of MACE in LOF allele carriers remained significantly higher even in high loading dose group (high loading dose: OR 1.72, 95% CI: 1.37 to 2.16, and routine loading dose: OR 2.22, 95% CI: 1.68 to 2.94, p for subgroup heterogeneity = 0.16). Subgroup analysis between three nationalities of China, Korea, and Japan demonstrated that the risk of MACE among Chinese LOF allele carriers was the greatest (OR: 2.28; 95% CI:1.91 to 2.73). In conclusion, among Asian populations with CAD undergoing stent implantation, CYP2C19 LOF allele carriers are at greater risk of adverse cardiovascular events and lower risk of bleeding compared with non-carriers. Genetic testing may be helpful for clinicians to personalize antiplatelet therapy especially in Asian population.     

Effects of CYP2C19 gene polymorphism on cure rates for Helicobacter pylori infection by triple therapy with proton pump inhibitor (omeprazole or rabeprazole), amoxycillin and clarithromycin in Japan

BACKGROUND: Omeprazole is mainly metabolized by cytochrome P450 2C19 (CYP2C19) in the liver. Rabeprazole, on the other hand, is mainly metabolized to thioether-rabeprazole via a non-enzymatic pathway and partially metabolized to demethylated-rabeprazole by CYP2C19 in liver CYP2C19 status may affect cure rate for Helicobacter pylori infection with proton pump inhibitor triple therapy. AIM: To investigate whether genetic polymorphism of CYP2C19 and selected proton pump inhibitors (omeprazole or rabeprazole) were associated with cure rate for Helicobacter pylori infection using triple therapy with omeprazole or rabeprazole, amoxicillin, and clarithromycin. METHODS: A total of 170 Helicobacter pylori-positive patients with chronic gastritis were randomized to receive one of the following Helicobacter pylori eradication regimens; OAC (omeprazole 20 mg bd, amoxycillin 750 mg bd and clarithromycin 400 mg bd for 1 week) and RAC (rabeprazole 20 mg bd, amoxycillin 750 mg bd and clarithromycin 400 mg bd for 1 week). The CYP2C19 genotype; wild-type or two mutant genes (ml in exon 5 and m2 in exon 4), or both, were identified by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In DAC regimen, cure rate (per protocol analysis) was 73.3% in homozygous extensive metabolizers, 86.1% in heterozygous extensive metabolizers, and 85.0% in poor metabolizers. In RAC regimen, the cure rate was 81.0% in homozygous extensive metabolizers, 82.9% in heterozygous extensive metabolizers, and 87.5% in poor metabolizers. Cure rate was not significantly different between the CYP2C19 genotypes in both regimens. CONCLUSION: Triple therapy with proton pump inhibitor (omeprazole or rabeprazole), amoxycillin, and clarithromycin is sufficiently effective in cure of Helicobacter pylori infection regardless of CYP2C19 status.     

CYP2C19基因多态性对老年人联用质子泵抑制剂与氯吡格雷的抑酸和抗血小板效果的影响

目的探讨细胞色素（cytochrome,CYP）2C19基因多态性对老年人联用质子泵抑制剂（proton pump inhibitator,PPI）与氯吡格雷的抑酸和抗血小板效果的影响。 方法选取2014年3月至2015年1月复旦大学附属华山医院老年病科收治的住院患者100例,均规律服用标准剂量PPI和（或）氯吡格雷。采用生物芯片法检测患者外周血CYP2C19基因型,根据基因型的不同代谢程度分组（强、中、弱代谢型组）,测定并比较不同代谢型组及各组内使用不同药物患者的胃液pH值、血小板抑制率（采用血栓弹力图检测）、PAG（M）（采用光学比浊法测定）。采用χ²检验分析CYP2C19基因型是否符合Hardy-Weinberg平衡;多组间比较应用单因素方差分析,进一步多重比较采用t检验;两组间的比较采用t检验。 结果强、中、弱代谢型组分别为42、46、12例;其中强代谢型组中单用PPI、单用氯吡格雷及PPI+氯吡格雷患者分别为16、14、12例,中代谢型组分别为22、10、14例,弱代谢型组分别为4、4、4例。CYP2C19等位基因的分布符合Hardy-Weinberg遗传平衡（χ²=0.49,P>0.05）。强、中、弱代谢型组间年龄、性别、血常规、肝肾功能、电解质、proBNP、血糖的差异均无统计学意义（均P>0.05）。强、中、弱代谢组中单用PPI患者血小板抑制率分别为（76.3±13.1）%、（55.9±19.1）%、（29.9%±6.1）%,差异有统计学意义（F=14.82,P<0.05）;单用氯吡格雷患者血小板抑制率分别为（76.3±13.1）%、（55.9±19.1）%、（29.9%±6.1）%,PAG（M）分别为（33.2±12.1）%、（35.2±13.8）%、（65.4±8.3）%,差异均有统计学意义（F=14.82、10.02,P<0.05或0.01）;PPI+氯吡格雷联用患者胃液pH值分别为3.66±0.7、4.5±0.5、5.0±0.7,血小板抑制率分别为（67.3±12.7）%、（40.6±25.8）%、（3.9±4.3）%,PAG（M）分别为（36.3±11.3）%、（56.2±24.0）%、（75.5%±12.3）%,差异均有统计学意义（F=9.33、15.46、7.08,P<0.05或0.01）。强代谢型组内,PPI+氯吡格雷与单用PPI患者胃液pH值的差异,以及PPI+氯吡格雷与单用氯吡格雷患者血小板抑制率及PAG（M）的差异均无统计学意义（t=-0.15、-1.70、0.67,均P>0.05）;中代谢型组内,PPI+氯吡格雷组与单用PPI患者胃液pH值的差异及PPI+氯吡格雷与单用氯吡格雷患者血小板抑制率的差异均无统计学意义（t=0.41、-1.05,P>0.05）,仅PPI+氯吡格雷与单用氯吡格雷患者PAG（M）的差异均有统计学意义[（56.2±24.0）%;（35.2±13.8）%;t=2.38,P<0.05]。弱代谢型组内,PPI+氯吡格雷与单用PPI患者胃液pH值的差异及PPI+氯吡格雷与单用氯吡格雷患者PAG（M）的差异无统计学意义（t=-0.13、1.18,均P>0.05）,仅PPI+氯吡格雷与单用氯吡格雷患者血小板抑制率的差异有统计学意义[（3.9±4.3）%,（29.9±6.1）%;t=-6.06,P<0.05]。应用经CYP450代谢药、CYP450酶抑制剂、不经CYP450酶代谢药患者胃液pH值分别为4.2±0.8、4.9±0.7、3.9±0.9,差异有统计学意义（F=3.12,P<0.05）。 结论CYP2C19基因多态性对老年人使用PPI的抑酸效果、氯吡格雷的抗血小板活性均有影响,PPI与氯吡格雷联合使用时可能相互减弱疗效,联用肝CYP450酶抑制剂会降低PPI的疗效。     

A Comparative Study on Endoscopic Ulcer Healing of Omeprazole Versus Rabeprazole with Respect to CYP2C19 Genotypic Differences

Omeprazole is mainly metabolized in the liver by CYP2C19, a genetically determined enzyme, while rabeprazole is mainly nonenzymatically degraded with a minor involvement by CYP2C19. We investigated the gastric ulcer healing effect of omeprazole versus rabeprazole evaluated endoscopically with reference to the different CYP2C19 genotypes. Eighty patients with active gastric ulcer were treated with a daily dose of 20 mg of omeprazole or 10 mg of rabeprazole. The endoscopic evaluation was performed at the baseline and 2- and 8-week posttreatment periods. The endoscopic improvement of gastric ulcer size and ulcer healing rates using a thin rubber disc with a diameter of 6 mm, were evaluated in relation to the CYP2C19 genotypic status. The mean 2-week posttreatment ulcer size value by rabeprazole did not significantly differ among the different CYP2C19 genotypes, whereas the mean value in the homozygous extensive metabolizer patients treated with omeprazole was significantly (P = 0.0057) greater than in those with rabeprazole. However, after the 8-week treatment, omeprazole and rabeprazole showed the similarly high healing rates of 87.8% (31/37) and 88.9% (32/36), respectively. Although both omeprazole and rabeprazole showed a high healing rate of gastric ulcer after the 8-week treatment period, the healing effect of rabeprazole appears to be relatively independent of the CYP2C19 status, resulting in an earlier repair of gastric mucosal damage evaluated endoscopically compared to that of omeprazole.     

CYP2C19基因多态性对埃索美拉唑三联疗法根除幽门螺杆菌疗效的影响

目的 研究CYP2C19(cytochrome P450 2C19)基因多态性对以埃索美拉唑为基础三联1周疗法的Hp根除率的影响.方法 选取101例Hp阳性的慢性胃炎或消化性溃疡患者,分成2组,分别进入埃索美拉唑联合阿莫西林与克拉霉素方案(EAC)或奥美拉唑联合阿莫西林与克拉霉素方案(OAC)进行1周根除治疗.治疗前采...     

CYP2C19基因多态性与质子泵抑制剂对消化性溃疡患者抑酸效应的关系

目的: 研究奥美拉唑(OME)、雷贝拉唑(RAB)及埃索美拉唑(ESO)对消化性溃疡患者的抑酸效应及与CYP2C19基因多态性的关系.方法:采用随机、开放和对照研究, 将消化性溃疡患者59例随机分为3组, 分别给予OME肠溶片(n = 19)、RAB肠溶片(n = 20)或ESO肠溶片(n = 20)各20 mg单剂量口服, 动态监测24 h胃内pH, 观察3种药物对患者的24 h和夜间抑酸效应及夜间酸突破(NAB)的影响. 用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法测定所有患者的CYP2C19基因型并分为强代谢型(EMs)和弱代谢型(PMs).结果: OME组、RAB组及ESO组EM和PM的比例分别为16/3, 17/3及17/3. OME 24 h抑酸与夜间抑酸效应(胃内pH>4的总时间和时间百分比)在PMs和EMs中的差异有显著性[24 h抑酸: (胃内pH>4的总时间: 10.65±2.3 h vs 7.22±2.1 h, P<0.05;时间百分比: 48.9±15.5 vs 32.5±12.6, P<0.05);夜间抑酸: (胃内pH>4的总时间: 3.67±1.2 h vs 2.25±1.2 h, P<0.05;时间百分比: 38.3±20.6 vs 20.8±18.9, P<0.05)]. 而RAB及ESO组24 h抑酸和夜间抑酸效应在PMs和EMs中的差异无显著性. RAB及ESO组NAB持续时间较OME组短(3.08±2.12 h, 2.98±2.73 h vs 4.50±2.86 h, 均P<0.05), NAB的pH高于OME组(2.15±0.70, 2.45±0.65 vs 1.15±0.31, 均P<0.001). RAB与ESO组间差异无显著性. 结论:奥美拉唑的抑酸效应受患者CYP2C19基因多态性影响;雷贝拉唑和埃索美拉唑的抑酸效应则受CYP2C19基因多态性影响极小, 3种PPIs的日间抑酸效应强于夜间, 雷贝拉唑和埃索美拉唑的抑酸效应优于奥美拉唑.     

CYP2C19酶与氯吡格雷抵抗

冠状动脉介入支架术后病人常规抗血小板的治疗,目前阿司匹林与氯吡格雷联合运用已成为支架术后抗血小板的常规诊疗方法。氯吡格雷需经CYP2C19代谢生成活性产物而发挥抗血小板聚集作用。但由于氯吡格雷抵抗发生支架内血栓事件逐渐增多,这一现象也受到人们的关注,冠状动脉介入支架术后病人服用氯吡格雷支架内血栓发生率与CYP2C19基因多态性是否有相关性。现就其研究现状做一综述。     

CYP2C19基因多态性与山西汉族冠心病及其类型的相关性

目的探讨CYP2C19基因多态性与山西汉族人群冠心病及其类型的关系。方法回顾性收集2017年1月至2018年6月于山西医科大学第二医院心内科住院的来自山西各地无血缘关系的汉族患者693例,根据冠状动脉造影结果、临床表现、心电图、心肌损伤标志物结果,分为冠心病组478例(包括稳定型心绞痛50例,不稳定型心绞痛157例,急性心肌梗死271例),无冠状动脉病变组(对照组)215例,进行CYP2C19基因型检测,分析基因型与等位基因在两组间及冠心病不同类型间分布有无差异。结果冠心病组CYP2C19~*1/~*2基因型分布频率高于对照组,差异有统计学意义(P=0.002);冠心病组CYP2C19~*2等位基因分布频率高于对照组,差异有统计学意义(P=0.011);对照组及冠心病三种不同类型间基因型、等位基因分布频率差异无统计学意义(P0.05)。Logistic回归结果示:排除性别、年龄、糖尿病、吸烟史、高血压等因素的影响后,携带有CYP2C19~*1/~*2基因型者患冠心病的风险增加(OR=1.838,95%CI 1.252～2.698)。结论 CYP2C19基因多态性是山西汉族冠心病发生的危险因素,但与冠心病的不同类型无相关性。