Sugimoto Mitsushige, Furuta Takahisa, Shirai Naohito, Ikuma Mutsuhiro, Hishida Akira, Ishizaki Takashi
First Department of Medicine, Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Clin Pharmacol Ther. 2006 Jul;80(1):41-50. doi: 10.1016/j.clpt.2006.03.007. Epub 2006 Jun 8.
Polymorphisms of proinflammatory cytokines, such as interleukin (IL) 1beta and tumor necrosis factor (TNF) alpha, are associated with individual differences in gastric mucosal inflammation and acid inhibition in response to Helicobacter pylori infection. We investigated whether inflammation-related cytokine polymorphisms would influence the eradication rates of H pylori by a triple-therapy regimen.
Three hundred sixty patients infected with clarithromycin-sensitive strains of H pylori were genotyped for IL1B -511, IL1RN, TNFA -857/-863/-1,031, IL10 -1,082/-819/-592, and CYP2C19 and underwent triple therapy for 1 week with a proton pump inhibitor (20 mg omeprazole, 30 mg lansoprazole, or 10 mg rabeprazole) twice daily, 400 mg clarithromycin twice daily, and 750 mg amoxicillin (INN, amoxicilline) twice daily. The influences of the previously mentioned polymorphisms on the eradication rates were analyzed.
The intention-to-treat-based total eradication rate was 83.6% (301/360). The logistic regression analysis revealed that polymorphisms of CYP2C19 and IL1B -511 were independently associated with the eradication rates, but other cytokine polymorphisms were not associated with these rates. The eradication rates in patients with IL1B -511 C/C, C/T, and T/T genotypes were 72.2% (70/97), 87.7% (164/187), and 88.2% (67/76), respectively (P = .0017). When patients were stratified by CYP2C19 genotype status, IL1B -511 genotype-dependent differences in eradication rates were observed in homozygous extensive metabolizers (EMs) but not in heterozygous EMs and poor metabolizers of CYP2C19. The eradication rate in homozygous EM patients with the IL1B -511 C/C genotype was quite low (51.1% [22/43]).
IL1B -511 polymorphism, but not IL1RN, TNFA, or IL10 polymorphism, is one of the determinants of triple therapy for clarithromycin-sensitive strains of H pylori in CYP2C19 homozygous EMs.
促炎细胞因子的多态性，如白细胞介素（IL）-1β和肿瘤坏死因子（TNF）α，与胃黏膜炎症及幽门螺杆菌感染后酸抑制的个体差异有关。我们研究了炎症相关细胞因子多态性是否会影响三联疗法根除幽门螺杆菌的成功率。
对360例感染克拉霉素敏感型幽门螺杆菌菌株的患者进行IL1B -511、IL1RN、TNFA -857/-863/-1031、IL10 -1082/-819/-592和CYP2C19基因分型，并接受为期1周的三联疗法，即每日2次服用质子泵抑制剂（20毫克奥美拉唑、30毫克兰索拉唑或10毫克雷贝拉唑）、每日2次服用400毫克克拉霉素以及每日2次服用750毫克阿莫西林（国际非专利药品名称，amoxicilline）。分析上述多态性对根除成功率的影响。
基于意向性治疗的总根除率为83.6%（301/360）。逻辑回归分析显示，CYP2C19和IL1B -511的多态性与根除成功率独立相关，但其他细胞因子多态性与这些成功率无关。IL1B -511 C/C、C/T和T/T基因型患者的根除率分别为72.2%（70/97）、87.7%（164/187）和88.2%（67/76）（P = 0.0017）。当根据CYP2C19基因型状态对患者进行分层时，在CYP2C19纯合子广泛代谢者（EMs）中观察到IL1B -511基因型依赖性的根除率差异，但在杂合子EMs和CYP2C19慢代谢者中未观察到。IL1B -511 C/C基因型的纯合子EM患者的根除率相当低（51.1% [22/43]）。
在CYP2C19纯合子EMs中，IL1B -511多态性而非IL1RN、TNFA或IL10多态性是克拉霉素敏感型幽门螺杆菌菌株三联疗法的决定因素之一。
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