幽门螺杆菌致病相关基因集群多态性的研究

Gene polymorphism of Helicobacter pylori cytotoxin associated genes cluster

目的基因多态性已逐渐成为幽门螺杆菌(Helicobacter pylori,Hp)新的研究热点。文中旨在研究临床Hp菌株中cagA、cagM、cagZ、cagⅠ-Ⅱ接点、IS605等cag致病岛(cag pathogenicity island,cagPAI)相关的遗传学位点的多样性分布及其与胃十二指肠疾病的关系。方法参照标准菌株NCTC11638序列设计引物,特异性PCR方法检测253株Hp菌株中,cagA、cagM、cagZ基因、cagⅠ-Ⅱ接点以及IS605等不同遗传学位点的分布情况。结果 253株临床分离的Hp菌株中,cagA基因的检出率为92.5%(234/253);cagM的检出率为86.2%(218/253);cagZ的检出率为66%(167/253);在慢性非萎缩性胃炎、消化性溃疡、胃癌中的检出率差异均无统计学意义(P>0.05)。仅5.1%(13/253)的Hp菌株中可检测到具有西方菌株特征的cagⅠ-Ⅱ接点的存在,提示中国大部分菌株中的cagⅠ-Ⅱ接点存在明显不同于西方菌株的结构形式;含西方菌株连续状态特征的cagPAI在消化性溃疡中13.3%(10/75)的检出率明显高于慢性非萎缩性胃炎中1.4%(2/146)的检出率(P<0.01)。IS605在慢性非萎缩性胃炎中51.4%(75/146)的检出率明显高于消化性溃疡中28%(21/75)的检出率(P<0.01)。结论cagPAI集群的序列结构具有丰富的基因多样性;cagA、cagM、cagZ等遗传学位点单独无一可作为临床Hp菌株的毒力标志;IS605的存在可能影响菌株的毒力发挥;cagⅠ-Ⅱ接点区域可能存在中国或东亚菌株的特征性结构。

Objective Gene polymorphism is becoming a focus in the studies of Helicobacter pylori （Hp）. The aim of this study was to observe the distribution of cagA, cagM, cagZ, cag I - II conjunction, and IS605, the genes localized in or related to the cag pathogenicity island （cag PAI） of Hp, and to investigate their association with gastroduodenal diseases. Methods The distribu- tion of cagA, cagM, cagZ, cag I -11 conjunction, and IS605 was detected by polymerase chain reaction （PCR） in 253 Hp strains from Chinese patients with gastroduodenal disease. The primers were designed based on the standard strain sequence NCTCl1638. Results Of the 253 clinical isolates, the detection rates of cagA, cagM, cagZ were 92.5% （234/253）, 86.2% （218/253） and 66% （ 167/253）, respectively. No loci of cagA, cagM, cagZ showed any relationship with chronic non-atrophic gastritis, peptic ulcer and gastric cancer （P 〉 0.05）. The conjunction of cag I - II characteristic of Western strains was detected in only 5.1% （ 13/253 ） of the Chinese isolates, indicating a strain structure different from that of the Western strain. The detection rate of the Western type cag I - II conjunction was significantly higher in the strains from peptic ulcer （ 10/75 ） than in those from chronic non-atrophic gastritis （2/146） （P 〈 0.01 ）, and so was the detection rate of IS605 in chronic non-atrophic gastritis than in peptic ulcer （75/146 vs 21/75,P 〈 0. 01 ）. Conclusion The cagPAl cluster sequence has an extensive gene polymorphism. None of cagA, cagM and cagZ can act alone as a virulence predictor of Hp. The presence of IS605 could af- fect the virulence of Hp. There may be a structure in the region of the cag I - II conjunction that is characteristic of Chinese or East Asian strains.