Ozdil Burhan, Akkiz Hikmet, Bayram Süleyman, Bekar Aynur, Akgöllü Ersin, Sandikçi Macit
Department of Gastroenterology, Cukurova University, School of Medicine, Adana.
Turk J Gastroenterol. 2010 Mar;21(1):23-8.
BACKGROUND/AIMS: Proton pump inhibitors are mainly metabolized by cytochrome P450 2C19 in the liver. Recently, some studies have shown that the acid suppressing effect of proton pump inhibitors are influenced by a functional polymorphism of cytochrome P450 2C19. The aim of the present study was to investigate the effect of cytochrome P450 2C19 polymorphism on Helicobacter pylori eradication in patients who received proton pump inhibitors based triple therapy.
We determined the incidence of cytochrome P450 2C19 genotypes and the effect of cytochrome P450 2C19 genotypes on Helicobacter pylori eradication rates in 105 patients with Helicobacter pylori-positive chronic gastritis. Upper endoscopic procedure and gastric biopsies were performed in all patients. Helicobacter pylori was demonstrated histologically. Lansoprazole, amoxicillin and clarithromycin twice a day for 14 days were prescribed for those found to be infected with Helicobacter pylori. More than one month after the medication, a 13C urea breath test was conducted to examine the success or failure of the eradication treatment. Cytochrome P450 2C19 polymorphism was analyzed by the polymerase chain reaction-restriction fragment length polymorphism method.
The genotypes of cytochrome P450 2C19 were classified into the three groups, as rapid extensive metabolizer, intermediate metabolizer and poor metabolizer. In our patient population, the frequencies of rapid extensive metabolizer, intermediate metabolizer and poor metabolizer were 72%, 23% and 5%, respectively. The eradication rate was 70.0% for rapid extensive metabolizer, 92% for intermediate metabolizer and 80% for poor metabolizer. The eradication rate was highest in intermediate metabolizer patients.
The present study confirmed the low eradication rate for rapid extensive metabolizer. Our findings provide evidence that the cytochrome P450 2C19 genotype is useful to predict the success of treatment. For the rapid extensive metabolizer group, alternative regimens can be tried to increase the Helicobacter pylori eradication rates.
背景/目的:质子泵抑制剂主要在肝脏中由细胞色素P450 2C19代谢。最近,一些研究表明质子泵抑制剂的抑酸作用受细胞色素P450 2C19功能多态性的影响。本研究的目的是调查细胞色素P450 2C19基因多态性对接受基于质子泵抑制剂的三联疗法的患者幽门螺杆菌根除的影响。
我们测定了105例幽门螺杆菌阳性慢性胃炎患者细胞色素P450 2C19基因型的发生率以及细胞色素P450 2C19基因型对幽门螺杆菌根除率的影响。所有患者均接受上消化道内镜检查和胃活检。通过组织学方法证实幽门螺杆菌感染。对那些被发现感染幽门螺杆菌的患者,给予兰索拉唑、阿莫西林和克拉霉素,每日两次,共14天。用药一个多月后,进行13C尿素呼气试验以检查根除治疗的成败。采用聚合酶链反应-限制性片段长度多态性方法分析细胞色素P450 2C19基因多态性。
细胞色素P450 2C19基因型分为三组,即快速代谢型、中间代谢型和慢代谢型。在我们的患者群体中,快速代谢型、中间代谢型和慢代谢型的频率分别为72%、23%和5%。快速代谢型的根除率为70.0%,中间代谢型为92%,慢代谢型为80%。中间代谢型患者的根除率最高。
本研究证实快速代谢型的根除率较低。我们的研究结果提供了证据表明细胞色素P450 2C19基因型有助于预测治疗的成功。对于快速代谢型组,可以尝试替代方案以提高幽门螺杆菌根除率。