Luo L L, Chen B, Shu X L, Zheng W, Long G, Jiang M Z
Gastrointestinal Laboratory, Children's Hospital, Zhejiang University School of Medicine,National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310052, China.
Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310052, China.
Zhonghua Er Ke Za Zhi. 2023 Jul 2;61(7):600-605. doi: 10.3760/cma.j.cn112140-20221230-01076.
To investigate the relationship between genetic polymorphisms of cytochrome P450 2C19 (CYP2C19) and the efficacy of (Hp) eradication therapy in children. 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 C 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. 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 (=124.00, <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 (=11.35, 0.010); those in IM genotype was significantly lower than that in PM genotype (=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) (=0.007 and 0.007, respectively). There was a significant difference in the efficacy of Hp eradication treatment among different genotypes (=9.72, =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 (=6.97, 0.018). 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.
探讨细胞色素P450 2C19（CYP2C19）基因多态性与儿童幽门螺杆菌（Hp）根除治疗疗效的关系。对2016年9月至2018年12月在浙江大学医学院附属儿童医院因恶心、呕吐、腹痛、腹胀、反酸、烧心、胸痛、呕血及黑便等胃肠道症状行胃镜检查且快速尿素酶试验（RUT）阳性的125例儿童进行回顾性队列研究。治疗前行胃窦黏膜Hp培养及药敏试验。所有患者均完成2周的标准化Hp根除治疗，并于治疗后1个月行C尿素呼气试验以评估疗效。分析RUT后胃黏膜DNA，检测CYP2C19基因多态性。儿童按代谢类型分组。结合Hp培养及药敏结果，分析儿童CYP2C19基因多态性与Hp根除治疗疗效的关系。行列表资料采用χ²检验，组间比较采用Fisher确切概率法。本研究共纳入125例儿童，其中男76例，女49例。这些儿童中CYP2C19基因多态性发现慢代谢型（PM）占30.4%（38/125），中间代谢型（IM）占20.8%（26/125），正常代谢型（NM）占47.2%（59/125），快代谢型（RM）占1.6%（2/125），超快代谢型（UM）占0。这些组间Hp培养阳性率差异有统计学意义（=124.00，<0.001）。此外，PM、IM、NM和RM基因型的Hp根除成功率分别为84.2%（32/38）、53.8%（14/26）、67.8%（40/59）和0，差异有统计学意义（=11.35，0.010）；IM基因型的根除成功率显著低于PM基因型（=0.011）。采用相同标准的三联Hp根除方案，IM型的Hp根除成功率为8/19，低于PM型（80.0%，24/30）和NM型（77.3%，34/44）（分别为=0.007和0.007）。不同基因型的Hp根除治疗疗效差异有统计学意义（=9.72，=0.008）。根据克拉霉素药敏结果，IM基因型在敏感组的Hp根除治疗成功率为4/15，耐药组为4/4（=6.97，0.018）。儿童CYP2C19基因多态性与Hp根除治疗疗效密切相关。PM型的根除治疗成功率高于其他基因型。
