CYP2C19基因多态性对PPI不良反应发生率的影响

[目的]分析CYP2C19基因多态性对质子泵抑制剂(PPI)不良反应发生率的影响。[方法]筛选服用PPI的患者1 167例,通过病历查询判断是否发生PPI相关的不良反应并采用全自动基因芯片检测系统对其CYP2C19基因型进行检测同时按基因型分为纯合快代谢、杂合快代谢和慢代谢。[结果]所有检测患者中,CYP2C19*1/*1型436例(占37.4%),CYP2C19*1/*2型487例(占41.7%),CYP2C19*1/*3型69例(占5.9%),CYP2C19*2/*2型134例(占11.5%),CYP2C19*3/*3型2例(占0.2%),CYP2C19*2/*3型39例(占3.3%),CYP2C19基因型与PPI不良反应发生率无明显联系(P0.05)。CYP2C19纯合快代谢型436例(占37.4%),杂合快代谢型556例(占47.6%),慢代谢型175例(占15%),CYP2C19代谢型与PPI不良反应发生率之间存在因果关系(P0.05)。代谢类型与不良反应发生类型无明显联系(P0.05)。[结论]CYP2C19基因多态性可影响PPI不良反应的发生,杂合快代谢型与慢代谢型的不良反应发生率均较纯合快代谢型升高,建议临床在应用PPI时应根据患者的CYP2C19基因型适当调整剂量以减少不良反应的发生。     

新疆地区维吾尔族、哈萨克族、回族和汉族人群CYP2C19基因多态性研究

[目的]探讨CYP2C19在新疆地区维吾尔族、哈萨克族、回族和汉族人群中的基因型及等位基因分布特征，为新疆地区各民族合理用药提供理论依据。 [方法]选取新疆医科大学第一附属医院就诊患者1908例，根据民族分为维吾尔族、哈萨克族、回族和汉族受试组，采用DNA微阵列芯片法检测CYP2C19基因多态性，比较不同民族CYP2C19等位基因、基因型和代谢型的分布差异性。[结果]新疆地区维吾尔族、哈萨克族、回族和汉族受试组CYP2C19的等位基因、基因型、代谢型分布差异均有统计学意义（P＜0.05）。根据等位基因判断：CYP2C19*1占68.11%；CYP2C19*2占27.59%；CYP2C19*3占4.3%；根据基因型判断：快代谢型占47.85%；中间代谢型占40.46%；慢代谢型占11.69%。哈萨克族受试组快代谢型基因频率显著高于其余三个民族；汉族受试组中间型基因频率显著高于其余三个民族；回族慢代谢型基因频率高于其余三个民族，差异均有统计学意义（P＜0.05）。 [结论]在新疆地区维吾尔族、哈萨克族、回族和汉族人群中，CYP2C19的等位基因、基因型、代谢型分布有显著差异。维吾尔族和哈萨克族人群以快代谢型为主，回族和汉族人群以中慢代谢型为主，对新疆地区各民族用药有一定指导意义。     

苏中苏南地区冠心病患者CYP2C19基因多态性分析研究

【目的】探讨冠心病患者CYP2C19基因在苏中苏南地区分布的多态性，将其分布在不同地域人群中进行比较，为冠心病患者合理使用药物提供指导作用。【方法】利用焦磷酸测序仪对CYP2C19 相关基因位点进行测序，并比较CYP2C19基因多态性在不同地区的分布差异。SPSS 26.0统计软件分析，χ2检验分析CYP2C19 基因突变符合 Hardy-weinberg 遗传平衡和进行组间比较。【结果】本研究共纳入2926例患者，根据基因型分为快代谢型（*1/*1），中代谢型（*1/*2、*1/*3）和慢代谢型（*2/*2、*2/*3和*3/*3），频率分别为：38.21%、45.80%和15.99%。冠心病患者的 CYP2C19 等位基因和基因型分布在不同性别之间无统计学差异（P＞0.05）。苏中苏南地区冠心病患者CYP2C19等位基因和代谢类型分布与北京、安徽、重庆、云南地区无显著性差异(P＞0.05)，而与陕西地区相比有显著性差异(P＜0.05)。【结论】苏中苏南地区冠心病患者 CYP2C19 基因多态性的分布存在差异，主要为中快代谢型，且不同性别间无明显差异，为冠心病患者精准用药具有指导作用。     

细胞色素P450酶2C19基因多态性与血小板高反应性相关性的研究

目的探讨急性冠状动脉综合征患者PCI术后细胞色素P450酶2C19(CYP2C19)基因多态性与血小板高反应性(HTPR)的相关性。方法选择急性冠状动脉综合征并接受PCI术的患者304例,根据二磷酸腺苷诱导的最大血小板聚集率是否大于50%分为HTPR组73例,非HTPR组231例。行CYP2C19*2、CYP2C19*3基因型检测,根据检测结果分为快代谢型、中间代谢型和慢代谢型。并利用最大血小板聚集率评价患者的血小板反应性。统计学分析CYP2C19基因多态性对血小板反应性的影响。结果 HTPR组快代谢型基因比例明显低于非HTPR组(28.8%vs 57.6%,P0.05),慢代谢型基因比例明显高于非HTPR组(13.7%vs 3.9%,P0.01)。慢代谢型患者最大血小板聚集率明显高于快代谢型和中间代谢型患者[(76.3±11.3)%vs(35.4±14.2)%和(45.1±15.8)%,P0.05]。结论 CYP2C19基因多态性对服用氯吡格雷患者的HTPR具有一定影响。慢代谢型患者最大血小板聚集率显著高于快代谢型和中间代谢型患者。     

泰安地区冠心病患者CYP2C19、ABCB1、PON1基因型分布与氯吡格雷抵抗风险的相关性

目的]研究泰安地区冠心病患者CYP2C19、ABCB1、PON1基因型分布特点及与氯吡格雷抵抗风险的相关性。 [方法]选取2019年1月─2020年3月在泰安市中心医院住院且服用氯吡格雷治疗的冠心病患者594例,运用荧光染色原位杂交技术检测CYP2C19*2(rs4244285)、CYP2C19*3(rs4986893)、CYP2C19*17(rs12248560)、ABCB1(rs1045642)、PON1(rs662)基因型。 [结果]泰安地区冠心病患者CYP2C19*2、CYP2C19*3、CYP2C19*17基因型主要是野生纯合型(GG),其中CYP2C19*2 GG基因型频率为48.0％,CYP2C19*3 GG基因型频率为89.6％,CYP2C19*17 CC基因型频率为97.0％;ABCB1基因型主要是突变杂合型(CT),基因型频率为46.8％;PON1基因型主要是突变杂合型(AG),基因型频率为47.1％。CYP2C19*2、CYP2C19*3、CYP2C19*17、ABCB1、PON1基因型分布、等位基因分布在男性患者与女性患者中的分布差异无统计学意义(P＞0.05)。泰安地区冠心病患者CYP2C19等位基因频率及代谢型分布存在显著的地区差异。在纳入研究的594名患者中,综合评价患者氯吡格雷抵抗风险度≥2的患者有287例,约占患者总数的48.3%,表明48.3%的患者常规剂量服用氯吡格雷后存在氯吡格雷抵抗。其中在风险度≥2的287例患者中,有46例CYP2C19代谢类型为正常代谢型,约占患者总数的7.7%。 [结论]泰安地区冠心病患者CYP2C19*2、CYP2C19*3、CYP2C19*17、ABCB1、PON1基因型存在多态性,ABCB1、PON1基因多态性会对约7.7%的患者用药指导结果有影响。     

CYP2C19基因多态性与冠心病患者PCI术后氯吡格雷抵抗的关系

目的:探讨CYP2C19基因多态性对冠心病患者经皮冠状动脉介入治疗(PCI)术后氯吡格雷抵抗(CR)的影响。方法:选择在我院接受治疗并进行PCI手术的冠心病患者100例,其中CR 24例,无氯吡格雷抵抗(NCR)76例。根据CYP2C19基因型,患者被分为快代谢型CYP2C19*1/*1 (49例),中间代谢型CYP2C19*1/*2(28例)和*1/*3 (11例),慢代谢型CYP2C19*2/*2 (9例)和*2/*3 (3例)。分析不同基因型与CR、最大血小板聚集率(MPA)、主要不良心血管事件(MACE)发生的关系。结果:以快代谢型CYP2C19*1/*1基因型为基础,中间代谢型CYP2C19*1/*2和*1/*3 (OR=4.16、5.03,P均0.05)及慢代谢型CYP2C19*2/*2和*2/*3 (OR=7.04、17.6,P均0.01)发生CR的风险显著增加,中间代谢型分别增加4.16和5.03倍,慢代谢型分别增加7.04和17.60倍;与快代谢基因型比较,中、慢代谢基因型的MPA和MACE发生率均显著增加(P0.05或0.01);CR组MACE发生率显著高于NCR组(20.8%比5.3%,P=0.02)。结论:CYP2C19基因多态性对冠心病患者PCI术后氯吡格雷抵抗有一定的影响,带有中、慢代谢基因型冠心病患者更易发生氯吡格雷抵抗以及有更高的最大血小板聚集率和主要不良心血管事件发生率。     

CYP2C19基因多态性对老年冠心病PCI术后抗血小板治疗的影响

目的探讨中国南方汉族人中CYP2C19基因多态性与冠心病(CHD)氯吡格雷治疗后血小板活性的关系。方法选取拟行冠脉介入术治疗的中国南方汉族老年CHD患者193例,均给予氯吡格雷300 mg负荷剂量,75 mg qd维持剂量。通过流式细胞仪检测血小板聚集率,采用聚PCR RFLP法基因型进行CYP2C19基因型检测。根据不同的基因型人群间氯吡格雷的药物代谢动力学特征把携带野生型基因(*1/*1)归为快代谢型,突变杂合型(*1/*2、*1/*3)为中间代谢型、突变纯合型(*2/*2、*2/*3、*3/*3)为慢代谢型。观察患者在服用氯吡格雷等药物治疗后7 d及14 d血小板聚集率的情况。结果野生型与中间代谢型、慢代谢型组间血小板聚集程度比较差异有统计学意义(P0.05)。中间代谢型、慢代谢型7 d组血小板活性降低程度显著优于7 d组,患者CYP2C19基因慢代谢型的比例为9.84%;心血管事件占8.08%,与野生型基因患者相比有差异(P0.05)。结论 CYP2C19基因突变与CHD PCI术后氯吡格雷治疗血小板活性有关。     

云南地区老年患者冠状动脉介入术后细胞色素P4502C19基因多态性及抗血小板研究

目的探讨云南地区老年PCI患者细胞色素P450(CYP)2C19基因多态性特征及其指导下的抗血小板个体化治疗对患者的临床影响。方法入选2014年10月~2015年10月确诊为急性冠状动脉综合征(acute coronary syndrome,ACS)并行PCI术的患者469例,根据是否以CYP2C19基因多态性指导氯吡格雷用药分为常规治疗组(238例)和个体化治疗组(231例),个体化治疗组根据患者是否存在CYP2C19*2或CYP2C19*3功能缺失等位基因分为正常代谢型组(81例)、中间代谢型组(135例)、慢代谢型组(15例),随访出院1个月时出血事件和心血管缺血事件的发生以及C反应蛋白(C-reactive protein,CRP)的变化情况。结果个体化治疗组出院1个月后出血事件明显增加(9.5%vs 5.9%,P=0.031)。个体化治疗组出院1个月后CRP水平明显低于常规治疗组[(8.7±4.9)mg/Lvs(11.4±3.7)mg/L,P=0.008]。CYP2C19基因多态性正常代谢型为35.1%,中间代谢型为58.4%,慢代谢型为6.5%。结论根据基因多态性指导抗血小板治疗对于CYP2C19基因多态性慢代谢型可能有助于减少急性及亚急性支架内血栓及降低CRP水平,但可能增加了出血事件。     

血浆细胞色素P4502C19基因多态性与皖北汉族急性冠脉综合征患者氯吡格雷抵抗及冠脉介入术后近期预后的关系

目的:探讨皖北汉族急性冠状动脉综合征(ACS)患者血浆细胞色素P4502C19(CYP2C19)基因多态性分布特征及其与氯吡格雷抵抗(CR)的关系,并评价其对接受经皮冠状动脉介入治疗(PCI)患者近期预后的影响。方法:入选298例住院并接受阿司匹林和氯吡格雷双联抗血小板治疗的皖北汉族ACS患者。采用基因芯片技术和荧光定量PCR检测每位患者CYP2C19基因的多态性,根据结果分为快代谢型(CYP2C19*1/*1)、中等代谢型(CYP2C19*1/*2,CYP2C19*1/*3)和慢代谢型(CYP2C19*2/*2,CYP2C19*2/*3,CYP2C19*3/*3)3组。采用光学比浊法检测每位患者服用氯吡格雷前和用药后7d的血小板聚集率(PAR),以用药前后差值≤10%定义为CR。所有患者均行PCI,计算血管病变支数和Gensini评分。对患者住院期间严密观察,出院后通过电话或门诊随访≥3个月。结果:慢代谢型组较中等代谢型组,中等代谢型组较快代谢型组发生CR的比例均增高(均P0.05)。3组冠状动脉病变支数和Gensini评分差异均无统计学意义。多因素Logistic回归分析显示,携带CYP2C19突变基因是ACS患者发生CR的独立预测因子(OR:2.122,P0.01)。随访3个月以上,慢代谢型组和中等代谢型组较快代谢型组有更高的心血管事件发生率(P0.05)。结论:皖北汉族ACS患者血浆CYP2C19基因多态性与CR的发生存在相关性,且基因突变增加了患者PCI术后心血管事件发生的风险,影响临床预后。     

细胞色素P450 2C19基因多态性与原发性肝细胞癌的相关性研究

细胞色素P450（CYP）2C19代谢美芬妥英的酶活性在人群中呈快代谢型和慢代谢型二态分布。突变型等位基因是CYP2C19基因多态性的分子生物学基础。目的：对原发性肝细胞癌（HCC）患者的CYP2C19等位基因进行基因分型．探讨CYP2C19基因多态性与原发性HCC的关系。方法：纳入48例原发性HCC患者和88名健康对照者。设计相应引物，以聚合酶链反应．限制性片段长度多态性（PCR-RFLP）方法检测CYP2C19ml和CYP2C19m2突变型等位基因．对两组基因多态性进行分析比较。结果：HCC组CYP2C19慢代谢型（ml／m1和ml／m2）发生率为25．0％（12例）．与健康对照组的11．4％（10例）相比差异有统计学意义（P〈0．05，OR=3116，95％CI：1140—7113）。结论：CYP2C19慢代谢型与原发性HCC之间存在相关性，可能增加人群对HCC的易感性。     

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.     

不同细胞色素P4502C19基因型肝病合并消化性溃疡患者泮托拉唑钠血药浓度测定

细胞色素P4502C19（CYP2C19）基因多态性对第一代质子泵抑制剂（PPI）的代谢有直接影响。CYP2C19的表达具有肝脏特异性。目的：观察不同CYP2C19基因型肝病合并消化性溃疡患者泮托拉唑钠代谢的差异，探讨肝脏病变对CYP2C19活性的影响。方法：合并消化性溃疡的2l例原发性肝癌患者和22例脂肪肝患者纳入研究，25名健康志愿者作为对照。受试者口服泮托拉唑钠40mg／d一周，分别于服药ld和7d后采血，以反相高效液相色谱法测定血浆泮托拉唑钠浓度。结果：服药7d后，健康对照组、脂肪肝组和原发性肝癌组CYP2C19强代谢者的血浆泮托拉唑钠浓度均显著低于弱代谢者（P〈0．05）。无论是强代谢者还是弱代谢者，服药7d后血浆泮托拉唑钠浓度均表现为原发性肝癌组〉脂肪肝组〉健康对照组（P〈O．05）。结论：CYP2C19活性与肝病严重程度呈负相关。终末期肝病患者泮托拉唑钠血药浓度明显升高，尤其是CYP2C19弱代谢者。     

Endoscopic Analysis of Gastric Ulcer after One Week's Treatment with Omeprazole and Rabeprazole in Relation to CYP2C19 Genotype

In Japanese healthy CYP2C19 extensive metabolizers, rabeprazole 10 mg shows a faster onset of action and stronger inhibition of acid secretion than does omeprazole 20 mg on the first 3 days of administration. We evaluated gastric ulcer improvement after 1 week's treatment with rabeprazole or omeprazole in relation to CYP2C19 polymorphism. A 6-mm rubber disc was placed temporarily at the side of the ulcer for measurement of the ulcer area. The improvement ratios of ulcer area in homozygous extensive metabolizers (homoEMs), heterozygous extensive metabolizers (heteroEMs) and poor metabolizers (PMs) treated with rabeprazole 10 mg were 60.8, 65.0 and 55.3%, respectively, and these values are not significantly different. Corresponding values with omeprazole 20 mg were 46.3, 61.7 and 63.2%, respectively, and the value of homoEMs was significantly smaller than that of heteroEMs. The improvement ratios with rabeprazole in homoEMs and heteroEMs were significantly greater than that with omeprazole in homoEMs.     

Cytochrome P450 2C19 polymorphism influences the preventive effect of lansoprazole on the recurrence of erosive reflux esophagitis

BACKGROUND: The efficacy of lansoprazole (LPZ) at inhibiting gastric acid secretion is influenced by cytochrome P450 2C19 (CYP2C19) polymorphism. The purpose of the present study was to investigate whether CYP2C19 polymorphism had an influence on the remission of erosive reflux esophagitis (RE) during maintenance therapy with LPZ. METHODS: Eighty-two Japanese patients with initial healing of erosive RE by 8 weeks of LPZ therapy were enrolled. As maintenance therapy, the patients were treated with LPZ (15 mg/day) for 6 months. The CYP2C19 genotype, Helicobacter pylori infection status, and serum pepsinogen (PG) I/II ratio were assessed before treatment. The patients were investigated for relapse by endoscopy at 6 months or when symptoms recurred. RESULTS: The proportion of patients in remission after 6 months was 61.5%, 78.0%, and 100% among homozygous extensive metabolizers (homo-EM), heterozygous EM (hetero-EM), and poor metabolizers (PM), respectively. The percentage of PM patients who remained in remission was significantly higher than that of homo-EM or hetero-EM. CONCLUSIONS: The efficacy of LPZ (15 mg/day) as maintenance therapy for erosive RE is influenced by CYP2C19 polymorphism.     

Interleukin-1beta genetic polymorphism influences the effect of cytochrome P 2C19 genotype on the cure rate of 1-week triple therapy for Helicobacter pylori infection

OBJECTIVES: Genetic polymorphism of interleukin (IL)-1beta is associated with differences in gastric acid suppression in response to Helicobacter pylori (H. pylori) infection. Thus, the polymorphism might affect H. pylori eradication therapy, as antibiotics used in treatment regimens may be acid sensitive. In this study, we examined the impact of IL-1beta genetic polymorphism on the cure rate of triple therapy for H. pylori in relation to cytochrome P (CYP) 2C19 genotype and antibiotic resistance. METHODS: A total 249 patients with peptic ulcer disease were randomized to receive one of the following regimens: amoxicillin and clarithromycin together with omeprazole, lansoprazole, or rabeprazole. CYP2C19 and IL-1beta-511 genetic polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The intention-to-treat-based overall cure rate was 74.3% (95% CI=68-79%). In the normal acid secretion IL-1beta genotype group, the cure rate among CYP2C19 poor metabolizers (93.3%, 95% CI=56-99%) was significantly higher than among subjects in the CYP2C19 homozygous (60.0%, 95% CI=38-78%) and heterozygous (63.6%, 95% CI=46-78%), i.e., extensive metabolizer, groups (p<0.05). In the low acid secretion IL-1beta genotype group, there was no difference in the cure rate among the CYP2C19 genotype groups. Multiple logistic regression analysis identified susceptibility to clarithromycin (p<0.0001) and CYP2C19 genotype status (p=0.03) as significant independent factors for treatment failure. CONCLUSION: IL-1beta genetic polymorphism, although not an independent factor in treatment outcome, influences the impact of the CYP2C19 genotype on the cure rate of 1-wk triple therapy for H. pylori infection.     

细胞色素P450 2C19基因多态性对雷贝拉唑药动学和药效学的影响

目的研究中国汉族人细胞色素P450(CYP)2C19基因多态性及其对雷贝拉唑药动学和药效学的影响。方法在110例中国汉族健康志愿者中,应用聚合酶链反应限制性片段长度多态性(PCRRFLP)的方法确定CYP2C19基因型,分为纯合子强代谢型、杂合子强代谢型和弱代谢型3种表现型。从中分层选择20例幽门螺杆菌感染阴性的受试者,口服雷贝拉唑20mg/d×8d。分别在服药后第1天(d1)和第8天(d8)应用高效液相色谱法测定雷贝拉唑血药浓度,采用24h胃内pH监测仪分析雷贝拉唑的抑酸效果。结果CYP2C19弱代谢型占11%。服用雷贝拉唑d1时的血药浓度时间曲线下面积(AUC)在纯合子强代谢型、杂合子强代谢型和弱代谢型间的比率为1.0、1.3和1.8;给药d8时的AUC在这三种基因型间的比率为1.0、1.1和1.7。同时监测和分析24h胃内pH>4的总时间、24hpH>4的时间百分比、24h胃内pH中位值和均值,这些参数在CYP2C19三种基因型间均差异无显著性。服用雷贝拉唑d1和d8的24h胃内pH监测的各参数比例(d1/d8)在85%～110%之间。结论中国汉族人中,CYP2C19基因多态性对雷贝拉唑的药动学和药效学无明显影响。雷贝拉唑抑酸作用迅速。     

Genetic Polymorphisms of CYP2D6 Oxidation in Patients with Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) consists of ulcerative colitis and Crohn’s disease, both of which are associated with increased colorectal cancer risk. The relationship between genetically determined polymorphic metabolism of exogenous substances by oxidation catalyzed by CYP2D6 isoenzyme and susceptibility to cancer has aroused great interest. We determined whether there was an association between susceptibility to inflammatory bowel disease and particularly to CYP2D6 genotypes. The study was carried out in 39 patients with IBD. The control group consisted of 129 healthy volunteers. The CYP2D6 genotypes were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method with DNA extracted from peripheral blood. Among 39 patients with inflammatory bowel disease, extensive metabolizer (EM) genotype constituted 97.4%. One patient (2.6%) was poor metabolizer with CYP2D6*4/CYP2D6*4 genotype. Results obtained in the inflammatory bowel disease group did not differ significantly from those of the control group. Although the odds ratio for EM metabolizers was about 3.8-fold greater in the group of patients with inflammatory bowel disease, this association was not statistically significant. This data also showed no overall statistically significant association between alleles and incidence risk of inflammatory bowel disease [odds ratio (OR) of 1.36 for CYP2D6*1 allele, 0.83 for CYP2D6*3 allele, and 0.74 for CYP2D6*4 allele]. The present results suggest that EM genotype may be the risk factor of inflammatory bowel disease. Future studies are needed to confirm our assumptions on larger group of patients.     

A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer

Purpose

Cytochrome P450 2C19 (CYP2C19) is clinically important for the metabolism of many therapeutic drugs. CYP2C19 has two main point mutation sites leading to low metabolic capacity. Several CYP enzymes are also important for the metabolism of chemical carcinogens, and several studies have reported associations between CYP polymorphism and cancer susceptibility. Speculating on a potential association between CYP2C19 polymorphism and cancer susceptibility, we conducted this study in two phases. Cell lines of various gastroenterological cancers were screened in the first phase. A clinical investigation was then conducted to confirm the association with the candidate cancer in the second phase.

Methods

Genetic polymorphism of CYP2C19 was investigated in a total of 114 cell lines of five gastroenterological cancers. Based on this screening investigation suggesting an association with biliary tract cancer, we conducted a related study by recruiting 65 patients with biliary tract cancer and 566 patients with benign diseases as controls.

Results

Among the 114 cell lines investigated, biliary tract cancer was suggested to be most strongly associated with poor metabolizers of CYP2C19. Among 65 patients with biliary tract cancer, 18 (28%) were poor metabolizers of CYP2C19, whereas 87 (15%) of 566 control patients were poor metabolizers. The age- and gender-adjusted odds ratios for intermediate and poor metabolizers regarding the risk of biliary tract cancer were 1.5 (95% CI: 0.8–3.0, P = 0.17) and 2.7 (1.3–5.9, P = 0.006) compared to extensive metabolizers.

Conclusions

A genetic polymorphism of CYP2C19 is associated with susceptibility to biliary tract cancer.     

Influence of CYP2C19 polymorphism and Helicobacter pylori status on the antisecretory effect of omeprazole in gastroesophageal reflux disease]

BACKGROUND/AIMS: The acid suppressive effect of omeprazole (OMP) is influenced by the metabolic capacity of gastric acid suppression, which is dependent on CYP2C19 polymorphism. The aim of this study was to determine the influence of CYP2C19 polymorphism and Helicobacter pylori (H. pylori) infection on the intragastric acid suppression of OMP. METHODS: Thirty one patients with gastroesophageal reflux disease were treated with a daily oral dose of 20 mg OMP for 28 days. Patients were genotyped for CYP2C19 polymorphism by polymerase chain reaction-restriction fragment length polymorphism and classified into three groups: homogenous extensive metabolizers (Ho-EMs), heterogenous extensive metabolizers (Ht-EMs) and poor metabolizer (PMs). H. pylori infection status were assessed before OMP treatment. Intragastric pH was monitored over twenty four-hours before (day 0) and after (day 29) the treatment with OMP. RESULTS: Twenty four-hour intragastric mean pH in the PMs group was significantly higher than those in Ho-EMs and Ht-EMs (5.3+/-1.3 vs. 2.8+/-0.6, 3.6+/-1.4) (p<0.005). Twenty four-hour intragastric mean pH after the administration of OMP in the H. pylori positive group was significantly higher than the H. pylori negative group (4.7+/-1.4 vs. 3.2+/-1.4) (p<0.001). There was no significant difference in acid suppressive activity of OMP between H. pylori positive and negative group according to CYP2C19 polymorphism. CONCLUSIONS: The acid suppressive effect of OMP on intragastric pH is dependent on CYP2C19 polymorphism and the H. pylori-infected status in patients with gastroesophageal reflux disease. H. pylori infection may play a role in enhancing the acid suppressive potential of OMP.