The clinical role of cytochrome p450 genotypes in Helicobacter pylori management
The clinical role of cytochrome p450 genotypes in Helicobacter pylori management
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DOI：
10.1111/j.1572-0241.2003.07427.x
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发表时间：
2003-05
影响因子：
9.8
通讯作者：
A. Sapone;D. Vaira;S. Trespidi;F. Perna;L. Gatta;A. Tampieri;Chiara Ricci;Giorgio Cantelli-Forti;M. Miglioli;Gian Luigi Biagi;Moreno Paolini
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文献类型：
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作者：
A. Sapone;D. Vaira;S. Trespidi;F. Perna;L. Gatta;A. Tampieri;Chiara Ricci;Giorgio Cantelli-Forti;M. Miglioli;Gian Luigi Biagi;Moreno Paolini
目的：探讨不同细胞色素P450 （CYP）基因型对幽门螺杆菌根除治疗的影响。方法：该研究纳入143名连续的意大利白人幽门螺杆菌感染患者，根据欧洲幽门螺杆菌研究组指南诊断并接受1周三联治疗。利用人类基因组DNA，对CYP2C19（*2和*3）和CYP3A4等位基因（*1B、*2和*3）进行聚合酶链反应-限制性片段长度多态性分析，并对扩增子进行测序。结果：根据内镜金标准，93例患者达到幽门螺杆菌根除。在CYP2C19基因型方面，50例患者均为纯合子或杂合子广泛代谢物（homEM或hetEM）。homEM携带者的表现明显不如hetEM携带者；homEM基因型在单因素/多因素分析中也可预测失败。CYP3A4多态性携带者的根除率与CYP2C19携带者相似。4例CYP3A4*2单一多态性患者均获得根除，仅有29%（5/17）的CYP3A4*1B携带者未被根除。在CYP2C19 hetEM亚组中携带CYP3A4多态性的9例患者全部治愈，提示CYP3A4和CYP2C19之间可能存在正协同作用。结论：这项关于不同CYP基因型对幽门螺杆菌治疗影响的首次药物基因组学研究表明，与亚洲人群一样，CYP2C19基因型模式可能也与接受包括奥美拉唑在内的幽门螺杆菌根除方案的白种人有关。CYP2C19和CYP3A4介导的有利药物相互作用的可能性有待研究。
OBJECTIVE:The aim of this pharmacogenomics study was to investigate the influence of different cytochrome P450 (CYP) genotypes in Helicobacter pylori eradication therapy.METHODS:The study involved 143 consecutive Italian Caucasian patients with H. pylori infection diagnosed and treated with 1-wk triple therapy according to European Helicobacter Pylori Study Group guidelines. Using human genomic DNA, CYP2C19 (*2 and *3) and CYP3A4 alleles (*1B, *2, and *3) were evaluated by polymerase chain reaction–restriction fragment length polymorphism assays and confirmed by sequencing the amplicons.RESULTS:According to the endoscopy-based gold standard, 93 patients achieved H. pylori eradication. Regarding CYP2C19 genotype, the 50 patients who remained infected were all homozygous or heterozygous extensive metabolizers (homEM or hetEM). Carriers of homEM fared significantly less well than those of hetEM; homEM genotype was also predictive of failure at univariate/multivariate analysis. Carriers of CYP3A4 polymorphisms achieved favorable eradication rates similar to patients bearing CYP2C19. All four patients with single CYP3A4*2 polymorphism achieved eradication, and only 29% (5/17) of all CYP3A4*1B carriers did not achieve eradication. All nine patients carrying CYP3A4 polymorphisms in the CYP2C19 hetEM subgroup were cured, suggesting the possibility of a positive synergism between CYP3A4 and CYP2C19.CONCLUSIONS:This first pharmacogenomics study on the influence of different CYP genotypes on H. pylori therapy suggests that, as in Asian populations, CYP2C19 genotype patterns are probably also relevant in Caucasians receiving H. pylori eradication regimens that include omeprazole. The possibility of a favorable drug interaction mediated by CYP2C19 and CYP3A4 requires investigation.