Ying J J, Shu X L, 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 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.
Zhonghua Er Ke Za Zhi. 2023 Sep 2;61(9):827-832. doi: 10.3760/cma.j.cn112140-20230328-00216.
To investigate the association between (Hp) virulence factor genotypes and the degree and activity of gastric mucosa pathological changes in pediatric gastroduodenal diseases. This retrospective cohort study was conducted from May 2020 to October 2020. The frozen strains of Hp, which were cultured with the gastric mucosa of 68 children with gastroscopy confirmed gastroduodenal diseases who visited the children's hospital of Zhejiang University School of Medicine from April 2012 to December 2014, were resuscitated. After extracting DNA from these Hp strains, PCR amplification and agarose gel electrophoresis were performed to determine the detection rate of cytotoxin-associated protein A (cagA),vacuolating cytotoxin A (vacA)(s1a、s1b/s2,m1/m2), outer inflammatory protein A (oipA),blood group antigen binding adhesin (babA),duodenal ulcer promoting protein A (dupA) genes; oipA genes were sequenced to determine the gene status. The patients were divided into different groups according to the findings of gastroscopy and gastric mucosa pathology. The detection rates of various virulence factor genotypes among different groups were compared using tests or Fisher's exact tests. The 68 Hp strains all completed genetic testing. According to the diagnostic findings of gastroscopy, the 68 cases were divided into 47 cases of superficial gastritis and 21 cases of peptic ulcer. Regarding the pathological changes of gastric mucosa, 8 cases were mild, and 60 cases were moderate and severe according to the degree of inflammation; 61 cases were active and 7 cases inactive according to the activity of inflammation. The overall detection rates of cagA, vacA, vacA s1/m2, functional oipA, babA2, and dupA virulence factor genes were 100% (68/68), 100% (68/68), 94% (64/68), 99% (67/68), 82% (56/68), and 71% (48/68), respectively. In the superficial gastritis group, their detection rates were 100% (47/47), 100% (47/47), 96% (45/47), 98% (46/47), 81% (38/47), and 70% (33/47), respectively; in the peptic ulcer group, their detection rates were 100% (21/21), 100% (21/21), 90% (19/21), 100% (21/21), 86% (18/21), and 71% (15/21), respectively. There was no statistically significant difference between the two groups (all >0.05). In the mild gastric mucosa inflammation group, the detection rates of the above six genotypes were 8/8, 8/8, 8/8, 7/8, 7/8, and 5/8, respectively; and in the moderate to severe inflammation groups, the detection rates were 100% (60/60), 100% (60/60), 93% (56/60), 100% (60/60), 82% (49/60), and 72% (43/60), respectively, with no statistically significant difference between the two groups (all >0.05). In the active inflammation group, the detection rate of six genotypes were 100% (61/61), 100% (61/61), 93% (57/61), 98% (60/61), 82% (50/61), and 72% (44/61), respectively; and in the inactive inflammation group, they were 7/7, 7/7, 7/7, 7/7, 6/7, and 4/7, respectively. Again, there was no statistically significant difference between the two groups (all >0.05). There was no statistically significant difference in the detection rate of combinations of 4 or 5 virulence factor genes among the different groups (all >0.05). CagA, vacA, vacA s1/m2, functional oipA, babA2, and dupA genes are not associated with superficial gastritis and peptic ulcer in children, or with the degree and activity of gastric mucosa pathological inflammation. Different gene combinations of cagA, vacA, oipA, babA2, and dupA have no significant effects on predicting the clinical outcome of Hp infection in children.
探讨幽门螺杆菌（Hp）毒力因子基因型与小儿胃十二指肠疾病胃黏膜病理改变程度及活动度之间的关联。本回顾性队列研究于2020年5月至2020年10月进行。复苏2012年4月至2014年12月期间在浙江大学医学院附属儿童医院就诊、经胃镜确诊为胃十二指肠疾病的68例患儿胃黏膜培养的Hp冻存菌株。从这些Hp菌株中提取DNA后，进行PCR扩增及琼脂糖凝胶电泳，以确定细胞毒素相关蛋白A（cagA）、空泡毒素A（vacA）（s1a、s1b/s2，m1/m2）、外炎性蛋白A（oipA）、血型抗原结合黏附素（babA）、十二指肠溃疡促进蛋白A（dupA）基因的检出率；对oipA基因进行测序以确定基因状态。根据胃镜及胃黏膜病理检查结果将患者分为不同组。采用检验或Fisher确切概率法比较不同组间各种毒力因子基因型的检出率。68株Hp菌株均完成基因检测。根据胃镜诊断结果，68例患儿分为浅表性胃炎47例和消化性溃疡21例。关于胃黏膜病理改变，根据炎症程度，轻度8例，中度和重度60例；根据炎症活动度，活动期61例，非活动期7例。cagA、vacA、vacA s1/m2、功能性oipA、babA2和dupA毒力因子基因的总体检出率分别为（68/68）100%、（68/68）100%、（64/68）94%、（67/68）99%、（56/68）82%和（48/68）71%。浅表性胃炎组中，它们的检出率分别为（47/47）100%、（47/47）100%、（45/47）96%、（46/47）98%、（38/47）81%和（33/47）70%；消化性溃疡组中，它们的检出率分别为（21/21）100%、（21/21）100%、（19/21）90%、（21/21）100%、（18/21）86%和（15/21）71%。两组间差异无统计学意义（均>0.05）。胃黏膜轻度炎症组中，上述6种基因型的检出率分别为8/8、8/8、8/8、7/8、7/8和5/8；中度至重度炎症组中，检出率分别为（60/60）100%、（60/60）100%、（56/60）93%、（60/60）100%、（49/60）82%和（43/60）72%，两组间差异无统计学意义（均>0.05）。炎症活动期组中，6种基因型的检出率分别为（61/61）100%、（61/61）100%、（57/61）93%、（60/61）98%、（50/61）82%和（44/61）72%；非活动期组中，分别为7/7、7/7、7/7、7/7、6/7和4/7。两组间差异同样无统计学意义（均>0.05）。不同组间4种或5种毒力因子基因组合的检出率差异无统计学意义（均>0.05）。CagA、vacA、vacA s1/m2、功能性oipA babA2和dupA基因与小儿浅表性胃炎及消化性溃疡无关，也与胃黏膜病理炎症的程度及活动度无关。CagA、vacA、oipA、babA2和dupA的不同基因组合对预测小儿Hp感染的临床结局无显著影响。
