Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Department of Molecular Biology and Genetics, Faculty of Science, University of South Bohemia, Branišovská 31, České Budějovice (Budweis), Czech Republic.
J Antimicrob Chemother. 2019 Jan 1;74(1):11-16. doi: 10.1093/jac/dky401.
Eradication of Helicobacter pylori is influenced by susceptibility to antimicrobial agents, elevated bacterial load and degree of acid inhibition, which can be affected by genotypes of drug-metabolizing enzymes [cytochrome P450 (CYP) 2C19 polymorphism]. Theoretically, the choice and dose of proton pump inhibitor may also influence the suppression of H. pylori infection. The CYP2C19 genotype has recently been found to have an impact on peptic ulcer healing, H. pylori eradication and therapeutic efficacy of proton pump inhibitors.
Here, we investigated the impact of the CYP2C19 genotype polymorphism and the success of triple therapy (fluoroquinolones/metronidazole/clarithromycin) on antibiotic-resistant strains in eradicating H. pylori in human subjects with non-ulcer dyspepsia (NUD), in human subjects with peptic ulcer disease (PUD) and in asymptomatic human subjects (positive and negative for H. pylori infection).
Based on the CYP2C19 genotypes, determined by Droplet Digital PCR (ddPCR) analysis, we found 11.2%, 62.5% and 26.3% corresponding to rapid metabolizers, intermediate metabolizers and poor metabolizers, respectively. However, we did not find any significant effect for homozygous ABCB1 or CYP2C192 and CYP2C193 alleles. We detected several participants heterozygous for both ABCB1 and CYP2C192, CYP2C193 and CYP2C1917 loci. The participants heterozygous for both ABCB1 and CYP2C192 and *3 loci should be defined as intermediate and poor metabolizers according to the haplotype analysis in the NUD, PUD and asymptomatic subjects.
Consequently, fluoroquinolones/metronidazole/clarithromycin-based triple therapies can be used to eradicate H. pylori infection, if one does not know the CYP2C19 genotype of the patient.
幽门螺杆菌的根除受抗菌药物敏感性、细菌载量和酸抑制程度的影响，而这些因素又受药物代谢酶（细胞色素 P450 [CYP] 2C19 多态性）的基因型影响。理论上，质子泵抑制剂的选择和剂量也可能影响 H. pylori 感染的抑制。最近发现 CYP2C19 基因型对消化性溃疡愈合、H. pylori 根除和质子泵抑制剂的治疗效果有影响。
本研究调查了 CYP2C19 基因多态性和三联疗法（氟喹诺酮/甲硝唑/克拉霉素）的成功率对非溃疡性消化不良（NUD）、消化性溃疡病（PUD）和无症状（H. pylori 感染阳性和阴性）人类受试者中抗生素耐药菌株根除 H. pylori 的影响。
根据通过液滴数字 PCR（ddPCR）分析确定的 CYP2C19 基因型，我们分别发现 11.2%、62.5%和 26.3%的受试者分别为快速代谢者、中间代谢者和弱代谢者。然而，我们没有发现 ABCB1 或 CYP2C192 和 CYP2C193 等位基因的纯合子有任何显著影响。我们检测到一些参与者在 ABCB1 和 CYP2C192、CYP2C193 和 CYP2C1917 位点均为杂合子。根据 NUD、PUD 和无症状受试者的单体型分析，ABCB1 和 CYP2C192 和 *3 位点均为杂合子的参与者应被定义为中间代谢者和弱代谢者。
因此，如果不知道患者的 CYP2C19 基因型，氟喹诺酮/甲硝唑/克拉霉素三联疗法可用于根除 H. pylori 感染。
