Section of Gastroenterology, Veterans Affairs San Diego Health System, La Jolla, California; Tennessee Valley Healthcare System, Nashville, Tennessee; Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville Tennessee; Division of Gastroenterology, University of California, San Diego, La Jolla, California.
Department of Medicine, New York University, New York, New York.
Gastroenterology. 2021 Nov;161(5):1443-1459. doi: 10.1053/j.gastro.2021.07.043. Epub 2021 Aug 3.
BACKGROUND & AIMS: Helicobacter pylori infects approximately 50% of individuals worldwide. Successful H pylori eradication is associated with reduced risk of gastric cancer and peptic ulcer disease, among other conditions. We hypothesized that host genetic determinants, especially those affecting gastric pH, might contribute to eradication therapy failure, particularly when treatment adherence and antibiotic susceptibility are confirmed. We aimed to conduct a meta-analysis of host genetic variants associated with H pylori eradication failure.
We searched the literature for studies comparing posttreatment H pylori eradication failure vs success (outcome) according to host genetic polymorphisms (exposure). Reference groups were defined according to genotypes (or corresponding phenotypes) hypothesized to be associated with successful eradication. We pooled estimates using a random-effects model and performed comprehensive sensitivity analyses.
We analyzed 57 studies from 11 countries; the vast majority analyzed CYP2C19 polymorphisms. Among individuals prescribed eradication regimens with proton pump inhibitors predominantly CYP2C19 metabolized, enhanced vs poor metabolizer phenotypes were associated with a 2.52-fold significantly higher likelihood of eradication failure and 4.44-fold significantly higher likelihood when treatment adherence and H pylori clarithromycin susceptibility (if relevant) were confirmed. There was no association between CYP2C19 variants and eradication failure if proton pump inhibitors less metabolized by or that bypass CYP2C19 metabolism were used. IL1B polymorphisms that are vs are not associated with less gastric acid suppression were associated with 1.72-fold significantly higher likelihood of eradication failure. There was no association between MDR1 polymorphisms and H pylori eradication failure. The certainty of evidence was moderate.
Based on meta-analysis, we identified host genetic polymorphisms significantly associated with H pylori eradication failure; host genetics might underlie eradication failure among treatment-adherent individuals with confirmed H pylori antibiotic susceptibility.
全球约有 50%的个体感染幽门螺杆菌。成功根除幽门螺杆菌与降低胃癌和消化性溃疡等疾病的风险相关。我们假设宿主遗传决定因素，尤其是影响胃内 pH 值的因素，可能导致根除治疗失败，尤其是在确认治疗依从性和抗生素敏感性的情况下。我们旨在对与幽门螺杆菌根除失败相关的宿主遗传变异进行荟萃分析。
我们检索了文献，以比较根据宿主遗传多态性（暴露）治疗后幽门螺杆菌根除失败与成功（结局）的研究。参考组根据假设与成功根除相关的基因型（或相应表型）定义。我们使用随机效应模型汇总估计值，并进行了全面的敏感性分析。
我们分析了来自 11 个国家的 57 项研究；绝大多数分析了 CYP2C19 多态性。在接受主要由 CYP2C19 代谢的质子泵抑制剂根除方案治疗的个体中，增强型与弱代谢型表型相比，根除失败的可能性显著增加 2.52 倍，在确认治疗依从性和幽门螺杆菌克拉霉素敏感性（如适用）时，根除失败的可能性显著增加 4.44 倍。如果使用代谢或绕过 CYP2C19 代谢的质子泵抑制剂较少，则 CYP2C19 变体与根除失败无关。与胃酸抑制作用较弱相关的 IL1B 多态性与根除失败的可能性显著增加 1.72 倍相关。MDR1 多态性与幽门螺杆菌根除失败无关。证据的确定性为中等。
基于荟萃分析，我们确定了与幽门螺杆菌根除失败显著相关的宿主遗传多态性；宿主遗传学可能是在确认对幽门螺杆菌抗生素敏感性的治疗依从性个体中根除失败的基础。
