重庆地区CYP2C19基因多态性对儿童幽门螺杆菌根除疗效的影响

Influence of CYP2C19 genetic polymorphism on the Helicobacter pylori eradication efficacy in children in Chongqing

目的探究重庆地区幽门螺杆菌(Hp)感染儿童CYP2C19基因代谢型分布及其与性别、年龄及疗效等方面的相关性,为重庆地区儿童Hp感染的根除提供合理的方案。方法前瞻性临床队列研究。选择重庆医科大学附属儿童医院2020年3月至7月疑诊为Hp感染并行胃镜检查的156例儿童,均进行13C-尿素呼气试验(13C-UBT)、快速尿素酶试验(RUT)及组织学检测,同时对Hp培养阳性的患儿(102例)应用聚集合酶链反应(PCR)-序列特异性引物分析方法进行CYP2C19基因检测及对2种抗生素(克拉霉素、阿莫西林)进行耐药性试验,根据基因检测结果将CYP2C19基因代谢型分为纯合子快代谢型(HomEM)、中间代谢型(HetEM)及慢代谢型(PM),观察奥美拉唑联合阿莫西林与克拉霉素(PAC)方案在不同代谢型中的根除结局。不符合正态分布的计量资料以中位数(M)表示,计数资料以率或构成比表示,组间比较采用χ^(2)检验,P<0.05为差异有统计学意义。结果1.共102例患儿Hp培养阳性,13C-UBT阳性率为97.1%(99/102),RUT阳性率为99.0%(101/102),组织学阳性率为90.2%(92/102)。2.102例Hp感染儿童中,HomEM占45.1%(46/102),HetEM占41.2%(42/102),PM占13.7%(14/102)。3.102例Hp感染儿童中,男50例,女52例,年龄3岁~17岁9个月(中位数9岁7个月),CYP2C19基因代谢型在不同性别及不同年龄患儿间的分布差异均无统计学意义(均P>0.05)。4.使用PAC方案者87例,Hp根除治疗初治失败者36例,其中HomEM 18例,HetEM 15例,PM 3例,根除治疗成功者51例,其中HomEM 21例,HetEM 21例,PM 9例,不同CYP2C19基因代谢型在PAC方案中的Hp根除疗效比较差异无统计学意义(P>0.05)。5.87例患儿中,45例患儿对克拉霉素敏感,其中37例患儿根除治疗成功,42例患儿对克拉霉素耐药,其中14例患儿根除治疗成功,克拉霉素耐药性与PAC方案中儿童Hp根除疗效比较差异有统计学意义(P<0.05)。不同CYP2C19基因代谢型在PAC方案中根除疗效比较差异无统计学意义(P>0.05)。结论未发现重庆地区Hp感染儿童CYP2C19基因代谢型与性别、年龄及目前的PAC方案根除疗效有相关性。

Objective To investigate the distribution of CYP2C19 genotypes in Helicobacter pylori(Hp)infected children in Chongqing and the correlation of genotypes with gender,age and efficacy,and to provide a reasonable plan for Hp eradication in children in Chongqing.Methods A prospective clinical cohort study was carried out on 156 children who were suspected of Hp infection and underwent gastroscopy in Children′s Hospital of Chongqing Medical University from March to July 2020.13C-urea breath test(13C-UBT),rapid urease test(RUT)and histological examination were made for all the children included.Meanwhile,for Hp-positive children,the CYP2C19 genotypes were detected by using the polymerase chain reaction(PCR)-sequence-specific primer method,and their sensitivity to Clarithromycin and Amoxicillin was assessed.According to the genetic testing results,the CYP2C19 genotypes were divided into homozygous extensive metabolizer(HomEM),heterozygous extensive metabolizer(HetEM)and poor metabolizer(PM).The eradication outcomes of proton pump inhibitor combined with Amoxicillin and Clarithromycin(PAC)in different genotypes were observed.The measurement data that did not conform to the normal distribution were expressed with the median(M),and the enumeration data were represented by the rate or the constituent ratio.The Chi-square test was used for comparison between groups,and P<0.05 indicated statistically significant difference.Results(1)A total of 102 children were Hp positive.Positive rates of 13C-UBT,RUT and histologic results were 97.1%(99/102),99.0%(101/102),and 90.2%(92/102),respectively.(2)Among the 102 Hp-infected children HomEM accounted for 45.1%(46/102),HetEM for 41.2%(42/102),and PM for 13.7%(14/102).(3)There were 50 males and 52 females in 102 Hp-infected children.The age range was 3 years to 17 years and 9 months(median:9 years and 7 months).There was no significant difference in the distribution of CYP2C19 genotypes between females and males and among children of different ages(all P>0.05).(4)In 87 cases treated with PAC regimen,36 cases failed to eradicated Hp in the initial treatment,including 18 cases of HomEM,15 cases of HetEM,and 3 cases of PM.Hp was eradicated successfully in 51 cases,including 21 cases of HomEM,21 cases of HetEM and 9 cases of PM.There was no statistically significant difference in the Hp eradication efficacy among children with different CYP2C19 genotypes treated by the PAC regimen(P>0.05).(5)Among the 87 children,45 children were sensitive to Clarithromycin,and 37 of them achieved successful Hp eradication.About 42 children were resistant to Clarithromycin,and Hp eradication was fulfilled in 14 of them.There was a statistically significant difference in the Hp eradication efficacy among Clarithromycin-resistant children treated by PAC regimen(P<0.05).Conclusions The CYP2C19 genotypes have no correlation with gender,age and Hp eradication efficacy of PAC in children with Hp infection in Chongqing.