幽门螺杆菌根除疗效与CYP2C19基因多态性的相关性分析研究

The Impact of Cytochrome P450(CYP 2C19) Genetic Polymorphisms on Helicobacter Pylori Eradication Rates

目的比较以埃索美拉唑(ESO)与兰索拉唑(LPZ)为基础的三联疗法根除幽门螺杆菌(Hp)的疗效与细胞色素氧化酶P450 2C19(CYP2C19)基因多态性的关系。方法选取^(13)C尿素呼气试验阳性或胃镜快速尿素酶试验检测阳性患者92例,随机分为ESO组51例和LPZ组41例,均应用阿莫西林和克拉霉素,疗程7天;使用微测序方法确定患者CYP2C19基因型;治疗结束后1个月行^(13)C尿素呼气实验检测Hp根除结果。结果 ESO组及LPZ组的Hp根除率分别为76.47%(39/51)、70.73%(29/41),差异无显著性(P>0.05)。根据CYP2C19基因型分析,弱代谢型(PM)、中间代谢型(IM)及快代谢型(UM)的Hp根除率分别为91.3%(21/23)、70.69%(41/58)和54.55%(6/11),PM型的Hp根除率高于UM型患者(P=0.043),而与IM型的根除率差异无显著性(P>0.05);UM型与IM型间差异无显著性(P>0.05)。ESO组中各基因型的Hp根除率差异无显著性(P>0.05)。LPZ组中UM型与PM型间差异有显著性(P=0.024)。结论以ESO为基础三联根除疗法的。Hp根除率个体差异小,不受CYP2C19基因多态性的影响;而以LPZ为基础三联1周疗法的Hp根除率个体差异大,受CYP2C19基因多态性的影响,UM型者Hp根除率低,PM型者Hp根除率高;CYP2C19基因型检测对幽门螺杆菌根除用药选择具有重要的参考价值。

Objective To investigate the efficacy of proton pump inhibitor （PPI）-based triple therapy with amoxicil- lin, clarlthromycin and either lansoprazole or esomeprazole in the eradication of Helicobaeter pylori（ H. pylori）and the impact of cytochrome P450（CYP2C19） genetic polymorphisms on the eradication rates. Method Pylori-positive patients were eligible to this study. Hp infection was proven by 13 C-UBT or rapid urease test. Patients were random- ly assigned to receive one of the two regimens ： clarithmycin 500 mg bid and amoxicillin 1000 mg bid together with either esomeprazole 20 mg Bid（ESO group 51 patients） or lansoprazole 30 mg Qd（LPZ group 41 patients）for 1 week. The CYP2C19 genotyping was determined by Minisequencing technique. The eradication rates of Hp were e- valuated by ~3C-UBT on the 28th day after completion of treatment. Result 92 patients completed the trial. The e- radication rates of Hp in ESO group and LPZ group were 76.47% （39/51） and 70.73% （29/41） respectively（P〉 0.05 ）. The eradication rates of H. pylori were 91.3% （21/23） 70.69% （41/58） and 54.55% （6/11） in poor metabolizer（PM）, intermediate metabolizer（IM） and ultrarapid metabolizer（UM）, respectively. Difference was significant between UM and PM group（P = 0. 043 ）, but not between UM and IM group （P〉0.05） ;IM and PM group（P〉0.05）. In ESO group, the eradication rates between PM, IM and EM were not significantly different, re- spectively（P〉0.05）. However in LPZ group, there were significant differences between UM and [M group （P = 0. 024 ）. Conclusion ESO and LPZ triple therapy could eradicate H. pylori effectively. The efficacy of esome- prazole-based triple therapy was less affected by the CYP2C19 genotype. The eradication rates of Hp in PM were higher than that in IM and EM group. CYP2C19 genotype detection is of important reference value in the drug choice of Helicobacter pylori eradication.