摘要
目的探讨CYP2C19基因多态性与儿童幽门螺杆菌(Hp)根治效果的关系。方法回顾性队列研究。研究对象为2016年9月至2018年12月因"恶心、呕吐、腹痛、腹胀、反酸、烧心、胸痛、呕血、黑便"等消化道症状就诊于浙江大学医学院附属儿童医院,且已进行胃镜检查的125例患儿。患儿快速尿素酶试验(RUT)阳性,治疗前胃窦黏膜进行Hp培养和药敏试验,经过2周规范Hp根除治疗,且1个月后查13C尿素呼气试验结果判断疗效。利用胃镜检查中常规进行RUT检测过的胃窦黏膜,提取组织DNA,进行CYP2C19基因多态性检测并根据代谢型分组,结合Hp培养和药敏结果,分析CYP2C19基因多态性与儿童Hp根除治疗效果的关系。行列分析采用χ^(2)检验,组间比较采用Fisher确切概率法。结果125例患儿中男76例、女49例,CYP2C19基因多态性分布频率为弱或慢代谢(PM)型30.4%(38/125),中间代谢(IM)型20.8%(26/125),正常代谢(NM)型47.2%(59/125),快代谢(RM)型1.6%(2/125),超快代谢(UM)型为0,不同基因型阳性率间差异有统计学意义(χ^(2)=124.00,P<0.001)。PM、IM、NM、RM型患儿Hp根除治疗成功率分别为84.2%(32/38)、53.8%(14/26)、67.8%(40/59)、0,各基因型Hp根除治疗成功率的差异有统计学意义(χ^(2)=11.35,P=0.010),IM型Hp根除治疗成功率低于PM型(P=0.011)。在相同标准三联Hp根除治疗方案前提下,IM型Hp根除治疗成功率为8/19,低于PM(80.0%,24/30)和NM型(77.3%,34/44)(P=0.007、0.007)。各基因型Hp标准三联方案根除治疗效果差异有统计学意义(χ^(2)=9.72,P=0.008)。结合克拉霉素药敏结果分析Hp根除治疗成功率,IM型敏感组为4/15,耐药组为4/4,差异有统计学意义(χ^(2)=6.97,P=0.018)。结论CYP2C19基因在儿童中存在多态性分布,且与儿童Hp根治疗效存在密切关系,PM型根除治疗成功率较高。
Objective To investigate the relationship between genetic polymorphisms of cytochrome P4502C19(CYP2C19)and the efficacy of Helicobacter pylori(Hp)eradication therapy in children.MethodsThe 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.ResultsOne 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(χ^(2)=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(χ^(2)=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(χ^(2)=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(χ^(2)=6.97,P=0.018).ConclusionsThe 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.
作者
罗玲玲
陈波
舒小莉
郑伟
龙高
江米足
Luo Lingling;Chen Bo;Shu Xiaoli;Zheng Wei;Long Gao;Jiang Mizu(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;Department of Gastroenterology and Pediatric Endoscopy Center,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 Pediatrics,the First People's Hospital of Wenling,Wenling317500,China)
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2023年第7期600-605,共6页
Chinese Journal of Pediatrics
基金
浙江省重点研发计划(2021C03064)。
关键词
基因
螺杆菌
幽门
儿童
Genes
Helicobacter pylori
Child
