Influences of proinflammatory and anti-inflammatory cytokine polymorphisms on eradication rates of clarithromycin-sensitive strains of Helicobacter pylori by triple therapy
Influences of proinflammatory and anti-inflammatory cytokine polymorphisms on eradication rates of clarithromycin-sensitive strains of Helicobacter pylori by triple therapy
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DOI：
10.1016/j.clpt.2006.03.007
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发表时间：
2006-07-01
影响因子：
6.7
通讯作者：
Ishizaki, Takashi
中科院分区：
文献类型：
--
作者：
Sugimoto, Mitsushige;Furuta, Takahisa;Ishizaki, Takashi
背景和目标。促炎细胞因子的多态性，例如白细胞介素（IL）IP和肿瘤坏死因子（TNF）α，与幽门螺杆菌感染引起的胃粘膜炎症和酸抑制的个体差异相关。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的幽门螺杆菌根除率。方法：对 360 例感染克拉霉素敏感幽门螺杆菌菌株的患者进行 IL1B - 511、ILIRN、TNFA -857/-863/-1031、IL10 -1082/-819/-592 和 CYP2C19 基因分型，并接受为期 1 周的质子泵抑制剂三联治疗（20 mg 奥美拉唑、30 mg 奥美拉唑）兰索拉唑或 10 毫克雷贝拉唑）每日两次，400 毫克克拉霉素每日两次，以及 750 毫克阿莫西林（INN，阿莫西林）每日两次。分析了前面提到的多态性对根除率的影响。结果。基于意向治疗的总根除率为83.6% (301/360)。逻辑回归分析显示，CYP2C19 和 IL1B -511 的多态性与根除率独立相关，但其他细胞因子多态性与这些速率无关。 IL1B - 5 11 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 = .0017)。当根据 CYP2C19 基因型状态对患者进行分层时，在纯合的强代谢者 (EM) 中观察到 IL1B -511 基因型依赖性的根除率差异，但在杂合 EM 和 CYP2C19 的弱代谢者中没有观察到。 IL1B -511 C/C 基因型纯合 EM 患者的根除率相当低 (51.1% [22/43])。结论。 IL1B -511 多态性，而不是 ILIRN、TNFA 或 IL10 多态性，是 CYP2C19 纯合 EM 中克拉霉素敏感幽门螺杆菌菌株三联疗法的决定因素之一。
Backgrounds and Aims. Polymorphisms of proinflammatory cytokines, such as interleukin (IL) I P 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. Methods: Three hundred sixty patients infected with clarithromycin-sensitive strains of H pylori were geno-typed for IL1B - 511, ILIRN, TNFA -857/-863/-1031, IL10 -1082/-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. Results. 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 - 5 11 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]). Conclusions. IL1B -511 polymorphism, but not ILIRN, TNFA, or IL10 polymorphism, is one of the determinants of triple therapy for clarithromycin-sensitive strains of H pylori in CYP2C19 homozygous EMs.