【CYP2C19基因多态性与儿童幽门螺杆菌根除治疗疗效的关系】。

L L Luo, B Chen, X L Shu, W Zheng, G Long, M Z Jiang
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引用次数: 0

摘要

目的:探讨儿童细胞色素P450 2C19 (CYP2C19)基因多态性与幽门螺杆菌(Hp)根除治疗效果的关系。方法:对2016年9月至2018年12月因恶心、呕吐、腹痛、腹胀、反酸、胃灼热、胸痛、吐血、黑黑等胃肠道症状就诊于浙江大学医学院附属儿童医院的胃镜检查且快速脲酶试验(RUT)阳性患儿125例进行回顾性队列研究。治疗前用胃窦粘膜进行Hp培养和药敏试验。所有患者均完成2周的标准化Hp根除治疗,1个月后进行13C尿素呼气试验,评价疗效。对胃黏膜经RUT处理后的DNA进行分析,检测CYP2C19基因多态性。按代谢类型分组。结合Hp培养及药敏结果,分析CYP2C19基因多态性与儿童Hp根治疗效的关系。行、列变量采用卡方检验,组间比较采用Fisher精确检验。结果:125名儿童被纳入研究,其中76名为男性,49名为女性。这些儿童CYP2C19基因多态性发现,不良代谢者(PM)占30.4%(38/125),中间代谢者(IM)占20.8%(26/125),正常代谢者(NM)占47.2%(59/125),快速代谢者(RM)占1.6%(2/125),超快速代谢者(UM)占0.06%。各组间Hp培养阳性率比较,差异均有统计学意义(χ2=124.00, Pχ2=11.35, P=0.010);IM基因型显著低于PM基因型(P=0.011)。在相同标准三联根除Hp方案下,IM型Hp根除成功率为8/19,低于PM(80.0%, 24/30)和NM (77.3%, 34/44) (P分别=0.007和0.007)。不同基因型对Hp的根除效果比较,差异有统计学意义(χ2=9.72, P=0.008)。根据克拉霉素药敏结果,IM基因型Hp根除治疗的成功率,敏感组为4/15,耐药组为4/4 (χ2=6.97, P=0.018)。结论:儿童CYP2C19基因多态性与Hp根除治疗的疗效密切相关。PM比其他基因型具有更高的根除治疗成功率。
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[The relationship between genetic polymorphism of CYP2C19 and the efficacy of Helicobacter pylori eradication therapy in children].

Objective: To investigate the relationship between genetic polymorphisms of cytochrome P450 2C19 (CYP2C19) and the efficacy of Helicobacter pylori (Hp) eradication therapy in children. Methods: The retrospective cohort study was conducted on 125 children with gastroscopy and positive rapid urease test (RUT) from September 2016 to December 2018 who presented to the Children's Hospital of Zhejiang University School of Medicine due to gastrointestinal symptoms including nausea, vomiting, abdominal pain, bloating, acid reflux, heartburn, chest pain, vomiting blood and melena. Hp culture and drug susceptibility test were carried out with gastric antrum mucosa before treatment. All the patients completed 2 weeks of standardized Hp eradication therapy and had 13C urea breath test 1 month after that, which was used to evaluate the curative effect. The DNA of gastric mucosa after RUT was analyzed and CYP2C19 gene polymorphism was detected. Children were grouped according to metabolic type. Combined with the results of Hp culture and drug susceptibility, the relationship between CYP2C19 gene polymorphism and the efficacy of Hp eradicative treatment was analyzed in children. Chi square test was used for row and column variables, and Fisher exact test was used for comparison between groups. Results: One hundred and twenty five children were enrolled in the study, of whom 76 were males and 49 females. The genetic polymorphism of CYP2C19 in these children found poor metabolizer (PM) of 30.4% (38/125), intermediate metabolizer (IM) of 20.8% (26/125), normal metabolizer (NM) of 47.2% (59/125), rapid metabolizer (RM) of 1.6% (2/125), and ultrarapid metabolizer (UM) of 0. There were statistically significant in positive rate of Hp culture among these groups (χ2=124.00, P<0.001). In addition, the successful rates of Hp eradication in PM, IM, NM and RM genotypes were 84.2% (32/38), 53.8% (14/26), 67.8% (40/59), and 0, respectively, with significant differences (χ2=11.35, P=0.010); those in IM genotype was significantly lower than that in PM genotype (P=0.011). With the same standard triple Hp eradicative regimen, the successful rate of Hp eradication for IM type was 8/19, which was lower than that of PM (80.0%, 24/30) and NM type (77.3%, 34/44) (P=0.007 and 0.007, respectively). There was a significant difference in the efficacy of Hp eradication treatment among different genotypes (χ2=9.72, P=0.008). According to the clarithromycin susceptibility result, the successful rate of Hp eradication treatment for IM genotype was 4/15 in the sensitive group and 4/4 in the drug-resistant group (χ2=6.97, P=0.018). Conclusions: The genetic polymorphism of CYP2C19 in children is closely related to the efficacy of Hp eradication treatment. PM has a higher successful rate of eradication treatment than the other genotypes.

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