上海地区幽门螺杆菌cagA基因3‘区和vacA基因的多态性分析及其临床意义

目的：探讨上海地区人群杆菌（Ｈ．ｐｙｌｏｒｉ）ｃａｇＡ基因３’区和ｖａｃＡ基因的多态性及其临床意义。方法：９９株Ｈ．ｐｙｌｏｒｉ菌株分离自１７例慢性浅表性胃炎（ＣＳＧ）、２１例慢性萎缩性胃炎（ＣＡＧ）、１９例胃溃疡（ＧＵ）、２３例十二指肠溃疡（ＤＵ）和１９例胃癌（ＧＣ）患者。用聚合酶链反应（ＰＣＲ）技术对Ｈ．ｐｙｌｏｒｉ菌株的ｃａｇＡ基因３’区和ｖａｃＡ基因基因信号序列及中间区等位基因进行扩增和检     

具有cagA、vacA基因的幽门螺杆菌感染与胃、十二指肠疾病的关系

为初步探讨南京地区具有ｃａｇＡ、ｖａｃＡ基因幽门螺杆菌（Ｈｐ）的感染状况以及ｃａｇＡ、ｖａｃＡ基因的存在与表达和胃、十二指肠疾病的关系，利用ＰＣＲ技术扩增ｃａｇＡ、ｖａ－ｃＡ基因，对１０４份临床分离Ｈｐ菌进行检测分析。结果：（１）消化性溃疡患者ｃａｇＡ＋、ｖａｃＡ＋Ｈｐ感染率高于慢性胃炎患者（χ２＝１０．６，Ｐ＜０．０１）；（２）ｃａｇＡ＋组胃炎炎症的急性活动程度重于ｃａｇＡ－组（χ２＝９．９９，Ｐ＜０．０１），而ｃａｇＡ十组肠上皮化生率与ｃａｇＡ－组间无显著差异（χ２＝１．６４，Ｐ＞０．０５）；（３）胃癌患者以ｃａｇＡ＋、ｖａｃＡ＋菌株及ｃａｇＡ－、ｖａｃＡ＋菌株感染多见，胃癌感染后者的６例均为腺癌。结果提示消化性溃疡患者以具有ｃａｇＡ、ｖａｃＡ基因的Ｈｐ感染多见；ｃａｇＡ基因的存在与表达可能与炎症的急性活动程度有关，而与肠化生无关；ｃａｇＡ、ｖａｃＡ基因的存在与表达可能均与肿瘤的形成有关，ｖａｃＡ基因是否与腺癌形成有关，有待研究。     

具有cagA,vacA基因的幽门螺杆菌感染与胃,十二指肠疾…

为初步探讨南京地区具有ｃａｇＡ，ｖａｃＡ基因幽门螺杆菌的感染状况以及ｃａｇＡ，ｃａｃＡ基因的存在与表达和胃，十二指肠疾病的关系，利用ＰＣＲ技术扩增ｃａｇＡ，ｖａｃＡ基因，对１０４份临床分离Ｈｐ基因进行检测分析。结果：（１）消化性溃疡患者ｃａｇＡ＾＋，ｖａｃＡ＾＋Ｈｐ感染率高于慢性胃炎患者，（２）ｃａｇＡ＾＋组胃炎炎症的急性活动程度重于ｃａｇＡ＾－组，而ｃａｇＡ＾＋组肠上皮化生率与ｃａｇＡ＾－组间无     

细胞毒相关抗原（cagA）基因在中国人幽门螺杆菌中的分布及其临床 …

目的 研究细胞毒素相关抗原（ｃａｇＡ）基因在幽门螺杆菌（Ｈp）菌株中的分布，从而 明确中国人感染Ｈｐ菌株的毒力状况。方法 采用特异性引物扩增Ｈｐ ｃａｇＡ基因的２９７ｂｐ片段，对７４个临床分离Ｈｐ菌株采用聚合酶链反应（ＰＣＲ）进行分型。同时收集患者的胃镜诊断及胃窦病理资料。结果 ９０．５％的Ｈｐ菌株含有ｃａｇＡ基因，其中消化性溃疡（ＰＵ）患者感染株ｃａｇＡ基因携带率（９４．９％）高于慢性胃炎患者（８     

中国幽门螺杆菌cagA克隆和基因序列分析

目的　了解和分析中国幽门螺杆菌（ Ｈｅｌｉｃｏｂａｃｔｅｒ ｐｙｌｏｒｉ, Ｈｐ）菌株细胞毒素相关基因Ａ（ｃａｇＡ） 的核苷酸序列特性．方法　从两位患胃溃疡儿童的胃粘膜中分离两株 Ｈｐ 菌株,用ＰＣＲ方法扩增ｃａｇＡ 基因的５○端和３○端的两个片段并作克隆和序列分析．结果　两株中国 Ｈｐ 菌株ｃａｇＡ 基因之间的同源性为９４ ％ ～９５ ％ ． 中国Ｈｐ 菌株与国外菌株相同区段比较,５○端的同源性为８９ ％ ～９２ ％ ,３○端的同源性为６９ ％ ．结论　中国Ｈｐ 菌株与国外Ｈｐ 菌株ｃａｇＡ 基因５○端序列部分区域的同源性较好,可以作为分子检测 Ｈｐ 感染的靶基因序列,而ｃａｇＡ 基因３○端序列部分区域的同源性较差,可以作为Ｈｐ 分子流行病学研究的靶基因序列．     

含cagA基因幽门螺杆菌感染与胃、十二指肠疾病的相关性研究

幽门螺杆菌（Ｈｐ）感染是引起胃、十二指肠疾病的重要病因。Ｈｐ感染可持续数十年甚至终生,但是,Ｈｐ感染人群大多无症状,只有少数人可致病,这主要是由于Ｈｐ菌株间毒力不同所致。含ｃａｇＡ基因（细胞毒素相关蛋白的基因）的菌株,无论表型和基因型都与无ｃａｇＡ基...     

细胞毒素相关抗原(cagA)基因在中国人幽门螺杆菌中的分布及其临床意义

目的研究细胞毒素相关抗原（ｃａｇＡ）基因在幽门螺杆菌（Ｈｐ）菌株中的分布，从而明确中国人感染Ｈｐ菌株的毒力状况。方法采用特异性引物扩增ＨｐｃａｇＡ基因的２９７ｂｐ片段，对７４个临床分离Ｈｐ菌株采用聚合酶链反应（ＰＣＲ）进行分型。同时收集患者的胃镜诊断及胃窦病理资料。结果９０．５％的Ｈｐ菌株含有ｃａｇＡ基因，其中消化性溃疡（ＰＵ）患者感染菌株ｃａｇＡ基因携带率（９４．９％）高于慢性胃炎患者（８５．７％），但二者差异无显著性（Ｐ＞０．０５）。病理资料显示，Ⅰ、Ⅱ型菌株均可引起胃窦的慢性炎症，但严重程度Ⅱ型菌株（ｃａｇＡ－）高于Ⅰ型（ｃａｇＡ＋，Ｐ＜０．０５），二者在致活动性胃炎、肠上皮化生、胃粘膜萎缩及淋巴滤泡形成方面比较，差异无显著性（Ｐ＞０．０５）。结论中国人感染ＨｐⅠ型菌株比例较西方国家高，但ｃａｇＡ基因尚不能作为区分Ｈｐ感染致不同胃肠道疾病的单一指标。     

幽门螺杜菌cagA,vacA基因的调查及其临床意义

目的 调查广州地区患者感染幽门螺杆菌（Ｈｐ）的细胞毒素相关基因（ｃａｇＡ）及空泡毒素基因（ｖａｃＡ）亚型的流行情况,探讨Ｈｐ ｃａｇＡ及ｖａｃＡ亚型与Ｈｐ相关性胃肠疾病间的关系。方法 自广州地区不同疾病患乾胃黏膜中分离得到１９１株Ｈｐ,抽提各株菌的总ＤＮＡ,采用特定引物对各株菌ｃａｇＡ３’端、ｖａｃＡ中间序列（ｍ）及信号序列（ｓ）进行ＰＣＲ检测。结果 广州地区Ｈｐ ｃａｇＡ阳性者占８５．３％（１６     

人胃粘膜分离的幽门螺杆菌菌株的基因型和表现型

幽门螺杆菌（Ｈｐ）感染与慢性活动性胃炎、溃疡病、胃腺癌或ＭＡＬＴ淋巴瘤相关。Ｉ型Ｈｐ菌株具有空泡毒素（ＶａｃＡ）和细胞毒素相关抗原（ＣａｇＡ），可能与引起特殊的胃病有关。近年的兴趣之一是发现与Ｌｅｗｉｓ~ｂ血型抗原结合的Ｈｐ粘附蛋白一粘附素。表达粘附素的Ｈｐ菌株含有功能性ＢａｂＡ２基因，而另一些菌株中相应ＢａｂＡ１基因缺少一个开放读码框而不能翻译。作者研究了溃疡病（ｎ＝１３）、胃腺癌（ｎ＝１１）、ＭＡＬＴ淋巴瘤（ｎ＝１１）和胃窦炎（ｎ＝１８）患者的Ｈｐ００２分离株，对这些疾病与ＶａｃＡ、ＣａｇＡ…     

幽门螺杆菌cagA基因株与胃癌p53,bcl—2表达的研究

目的　通过研究幽门螺杆菌（Ｈｐ）及细胞毒蛋白相关基因Ａ 株〔ｃａｇＡ（＋ ）株〕感染与胃癌组织ｐ５３、ｂｃｌ２ 表达的相互关系，以探讨Ｈｐ 的可能致癌机制。　方法　聚合酶链反应（ＰＣＲ）检测９２ 例胃癌和２４ 例浅表胃炎组织石蜡标本Ｈｐ 和ｃａｇＡ（＋ ）株感染。用免疫组化方法检测全部标本的ｐ５３、ｂｃｌ２ 表达。　结果　（１）Ｈｐ 感染在胃癌和浅表胃炎病例间差异无显著性（７９４％ 及６６７％ ，Ｐ＞ ００５），而ｃａｇＡ（＋ ）株感染前者高于后者（９３２％ 及５００％ ，Ｐ＜ ００１）；（２）ｐ５３、ｂｃｌ２ 的表达在Ｈｐ（＋ ）与Ｈｐ（－ ）组之间差异无显著性，而ｃａｇＡ（＋ ）株感染组均显著高于ｃａｇＡ（－ ）株组（Ｐ＜００１）。　结论　胃癌的发生可能与不同Ｈｐ 菌株感染有关。产生细胞毒素的Ｈｐ 菌株〔ｃａｇＡ（＋ ）株〕与胃癌关系更密切，它可能是导致ｐ５３ 基因突变和ｂｃｌ２基因过度表达的原因之一。     

Polymerase chain reaction based analysis of the cytotoxin associated gene pathogenicity island of Helicobacter pylori from saliva: an approach for rapid molecular genotyping in relation to disease status

BACKGROUND AND AIMS: The genetic composition of the intricate cytotoxin associated gene pathogenicity island (cag PAI) of Helicobacter pylori is known to significantly influence the outcome of the disease. Hence, analysis of complete cag PAI of H. pylori isolated from saliva would be of immense importance in standardizing saliva as a reliable non-invasive diagnostic specimen and also to evaluate the type of H. pylori infection. The aim of the present study was to analyze the genes of cag PAI of H. pylori for their presence and correlating them with the disease status of the patients. METHODS: One hundred and twenty patients (55 duodenal ulcer [DU], 25 gastric ulcer and 40 non-ulcer dyspepsia [NUD]) were investigated for the present study. Eight pairs of oligonucleotide primers (cagA1, cagA2, cagAP1, cagAP2, cagE, cagT, LEC1 and LEC2) of five different loci; cagA, cagA promoter region, cagE which represents cagI region, cagT and LEC representing cagII were used to detect the presence of the cag PAI genes by polymerase chain reaction. RESULTS: The comprehensive analysis of the genes constituting cag PAI showed almost equivalent prevalence of all the genes between both the study groups (ulcer and NUD) included. Little significant difference was found in the percentage distribution in both the clinical groups. cagE and cagT were found in a larger proportion of the ulcer group (92.5% and 96.2%) compared with the NUD group (77.5% and 85%), respectively. CONCLUSION: Saliva could be efficiently used as a non-invasive source for H. pylori and cagT might be an important locus of the cag PAI, thus greatly influencing the disease condition of the subjects.     

Clinical presentation in relation to diversity within the Helicobacter pylori cag pathogenicity island

OBJECTIVE: This study investigated the genetic diversity of the cag pathogenicity island (PAI) in Helicobacter pylori (H. pylori) in relation to clinical outcome and interleukin (IL)-8 production. METHODS: Seven genes in the cag PAI (cagA, cagE, cagG, cagM, cagT, open reading frame 13 and 10) were examined by polymerase chain reaction and Southern blot hybridization using H. pylori from 120 patients with different presentations (duodenal ulcer, gastric cancer, gastritis alone). IL-8 production from AGS cells (gastric cancer cell line) cocultured with H. pylori was measured by ELISA. RESULTS: An intact cag PAI was present in 104 (87%) isolates, and five (4%) had deletions within the cag PAI; 11 (9%) lacked the entire cag PAI. Clinical isolates containing the complete cag PAI induced a greater secretion of IL-8 as compared with those without the cag PAI (3048 +/- 263 vs 480 +/- 28 pg/ml, p < 0.001). Deletion of only cagG reduced IL-8 secretion by two thirds. Deletions of more than one locus reduced IL-8 secretion to background. A similar proportion of H. pylori from patients with gastritis, duodenal ulcer, or gastric cancer had intact cag PAI (88%, 88%, and 85%, respectively). Although the presence of cagG was a better predictor of the presence of an intact cag PAI than cagA or cagE, the presence or absence of any of these genes had no association with clinical presentation. CONCLUSION: Although the cag PAI plays an important role in IL-8 production, clinical presentation cannot be predicted by the presence of an intact cag PAI or any of these seven cag PAI genes.     

Gene distribution of cagⅡ in Helicobacter pylori-infected patients of Zhejiang Province

AIM: To determine the prevalence of genotypes of cagⅡin Helicobacter pylori ( H pylori)-infected patients in Zhejiang Province and investigate the relationship between these genotypes and the types of gastroduodenal diseases.METHODS: One hundred and seventy one clinical isolates were collected from 70 chronic superficial gastritis, 31 chronic atrophic gastritis, 41 gastric ulcer, 21 duodenal ulcer, 3 gastric and duodenal ulcer, and 5 gastric adenocarcinoma patients. Polymerase chain reaction assays were performed for analysis of cagT, ORF13 and ORF10 genes in the cagⅡ region.RESULTS: Of 171 Hpyloriisolates from Zhejiang patients,159(93.0%) were positive for all the three loci. One isolate (0.6%) was negative for all the three loci, and 11(6.4%) were partially deleted in cagⅡ. The positive rates of cagT,ORF13and ORF10genes were 97.1%, 94.7% and 99.4%,respectively. In the strains isolated from the patients with diseases including chronic superficial gastritis, chronic atrophic gastritis, gastric ulcer and duodenal ulcer, the sitive rates of cagTwere 95.7%, 100.0%, 95.1% and 100.0%, respectively. The positive rates of ORF13 were 94.3%, 93.5%, 95.1% and 100.0%, respectively. The sitive rates of ORF10 were 98.6%, 100.0%, 100.0% and 100.0%, respectively. The three genes were all positive in the three H pylori strains isolated from the patients with both gastric and duodenal ulcer. In the five strains isolated from the patients with gastric adenocarcinoma,only one isolate was negative for ORF13. There were no significant differences of the cagT, ORF13and ORF10genes among the different gastroduodenal diseases including chronic superficial gastritis, chronic atrophic gastritis,gastric ulcer, duodenal ulcer, both gastric and duodenal ulcer and gastric adenocarcinoma (X2=3.098, P＞0.05 for cagT; X2=3.935, P＞0.05 for ORF13 and X2=6.328, P＞0.05for ORF10).CONCLUSION: The cagⅡis not a uniform and conserved entity. Although the genes in cagⅡ are highly associated with the gastroduodenal diseases, the clinical outcome of Hpylori infection is not reliably predicted by the three genes in cagⅡin patients from Zhejiang Province.     

上海地区幽门螺杆菌cagA基因3’区和vacA基因的多态性分析及其临床意义

探讨上海地区人群中幽门螺杆菌（H．pylori）cagA基因3’区和vacA基因的多态性及其临床意义。方法：99株H．pylori菌株分离自17例慢性浅表性胃炎（CSG）、21例慢性萎缩性胃炎（CAG）、19例胃溃疡（GU）、23例十二指肠溃疡（DU）和19例胃癌（GC）患者。用聚合酶链反应（PCR）技术对H．pylori菌株的cagA基因3’区和vacA基因信号序列及中间区等位基因进行扩增和检测。结果：99株H．pylori菌株中84株（84．8％）cagA基因阳性,其3’区产物大小均约650bp,属A型。vacA基因信号序列仅检出sla型,见于从94．1％（16／17）的CSG、952％（20／21）的CAG、89．5％（17／19）的GU、87．00（20／23）的DU和89．5％（17／19）的GC患者中分离的菌株（P＝0．87）;中间区等位基因仅检出m2型,见于从70．6％（12／17）的CSG、71．4％（15／21）的CAG、63．20（12／19）的GU、73．9％（17／23）的DU和57．9％（11／19）的GC患者中分局的菌株（P＝0．72）。结论：上海地区人群中H．pylori菌株的cagA基因3’区相对保守;绝大多数vacA基因属sla／m2型。本研究结果不支持这些基因的多态性与H．pylori感染临床结局相关的观点。     

Gene distribution of cagⅡ in Helicobacter pylori-infected patients of Zhejiang Province

AIM: To determine the prevalence of genotypes of cagⅡ in Helicobacter pylori( H pylon)-infected patients in Zhejiang Province and investigate the relationship between these genotypes and the types of gastroduodenal diseases.METHODS: One hundred and seventy one clinical isolates were collected from 70 chronic superficial gastritis, 31 chronic atrophic gastritis, 41 gastric ulcer, 21 duodenal ulcer, 3 gastric and duodenal ulcer, and 5 gastric adenocarcinoma patients. Polymerase chain reaction assays were performed for analysis of cagT, ORF13 and ORF10 genes in the cagⅡ region.RESULTS: Of 171 Hpyloriisolates from Zhejiang patients,159(93.0%) were positive for all the three loci. One isolate (0.6%) was negative for all the three loci, and 11(6.4%) were partially deleted in cagⅡ. The positive rates of cagT,ORF13 and ORF10 genes were 97.1%, 94.7% and 99.4%,respectively. In the strains isolated from the patients with diseases including chronic superficial gastritis, chronic atrophic gastritis, gastric ulcer and duodenal ulcer, the sitive rates of cagT were 95.7%, 100.0%, 95.1% and 100.0%, respectively. The positive rates of ORF13 were 94.3%, 93.5%, 95.1% and 100.0%, respectively. The sitive rates of ORF10 were 98.6%,100.0%,100.0% and 100.0%, respectively. The three genes were all positive in the three H pylori strains isolated from the patients with both gastric and duodenal ulcer. In the five strains isolated from the patients with gastric adenocarcinoma,only one isolate was negative for ORF13. There were no significant differences of the cagT, ORF13 and ORF10 genes among the different gastroduodenal diseases including chronic superficial gastritis, chronic atrophic gastritis,gastric ulcer, duodenal ulcer, both gastric and duodenal ulcer and gastric adenocarcinoma (χ^2=3.098, P＞0.05 for cagT;χ^2=3.935, P＞0.05 for ORF13 and χ^2=6.328,P＞0.05 for ORF10).CONCLUSION: The cagⅡ is not a uniform and conserved entity. Although the genes in cagⅡ are highly associated with the gastroduodenal diseases, the clinical outcome of Hpyloriinfection is not reliably predicted by the three genes in cagⅡ in patients from Zhejiang Province.     

Geographic differences and the role of cagA gene in gastroduodenal diseases associated with Helicobacter pylori infection.

Helicobacter pylori (H. pylori) is the major causal agent of gastritis, peptic ulcer and gastric cancer. Several bacterium genes seem to be involved in the pathogenicity mechanism. One of them, the cagA gene, has been extensively studied and characterized. In this article we have carried out a study of characteristics and genetic variability of cagA gene in different geographic areas of the world. At the same time, we have summarized several studies that evaluate possible relation of cagA with gastroduodenal diseases associated by H. pylori infection. In our study we found that the presence of the cagA gene has been confirmed in more than 60% H. pylori strains distributed throughout the world. The prevalence of cagA genotype is of 65.4% in gastritis patients, 84.2% in patients with peptic ulcer and 86.5% in those with gastric cancer. It shows a high genetic variability of cagA associated with gastroduodenal diseases that could serve as a virulence marker in H. pylori infected subjects. However, the high prevalence of H. pylori cagA positive strains in some geographic areas does not confirm the strong association between cagA and virulence of strains as described in other countries. Nowadays, cagA gene is considered as a marker for the presence of cag pathogenicity island (cag-PAI) in H. pylori genoma. This region contains several genes that has been involved with the production of cytokines that results in an increased inflammation of host gastric mucosa, but its function is unknown. Probably, others bacterium factors, such as susceptibility host and environmental cofactors could influence in the risk of developing different gastroduodenal diseases associated with H. pylori infection.     

Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA and babA2 genotypes in Thai dyspeptic patients.

OBJECTIVES: To investigate the prevalence of the vacA, cagA, cagE, iceA, and babA2 genotypes in Helicobacter pylori strains isolated from Thai dyspeptic patients, and to determine whether any correlation exists between these genotypes and clinical manifestations. METHODS: Helicobacter pylori was examined in 112 patients (62 with non-ulcer dyspepsia (gastritis), 34 with peptic ulcer disease, and 16 with gastric cancer (GCA)), detected by culture or direct detection from gastric biopsies. Allelic variants of the vacA, cagA, cagE, iceA, and babA2 genotypes were identified by using the polymerase chain reaction. RESULTS: The positive rates for the vacAs1, vacAs2, cagA, cagE, iceA1, iceA2, and babA2 genes in H. pylori of dyspeptic patients were 100%, 0%, 98.2%, 88.4%, 45.5%, 33.1%, and 92%, respectively. The allelic variant vacAs1m1 was more prevalent (58%) than vacAs1m2 (42%). The cagA and cagE genes were commonly found together (87.5%). The most predominant genotypes were vacAs1m1, cagA, cagE, iceA1, and babA2. The various genes alone or in combination had no statistically significant association with the clinical outcomes (p>0.05). CONCLUSION: Neither single gene nor combination of vacA, cagA, cagE, iceA, and babA2 genes was significantly helpful in predicting the clinical outcome of H. pylori infection in Thai patients. The high prevalence of these genes in H. pylori isolated from Thai patient groups suggests that H. pylori strains are geographically dependent.     

Prevalence and genetic diversity of cagD, cagE, and vacA in Helicobacter pylori strains isolated from Japanese patients

BACKGROUND: Although cagD and cagE (cagDE) identified upstream of cagA have been shown to be involved in the induction of interleukin (IL)-8 expression, the relationship between cagDE status and gastroduodenal diseases still remains to be examined. Thus we investigated prevalence and genetic diversity of cagD, cagE, and vacA in Helicobacter pylori strains isolated from patients with peptic ulcer or gastritis. METHODS: We analyzed 73 H. pylori strains isolated from Japanese patients (gastritis (GA), 15; gastric ulcer (GU), 28; duodenal ulcer (DU), 23; GU and DU, 7). The presence of cagDE was evaluated by polymerase chain reaction (PCR) and Southern hybridization. The vacA genotype was examined by PCR, using type-specific primers. RESULTS: cagDE was present in 13 (86.7%) of 15 patients with GA, 26 (92.9%) of 28 patients with GU, 21 (91.3%) of 23 patients with DU, and 6 (85.7%) of 7 patients with GU and DU (P = 0.89). vacA signal sequence type s1 was found in 14 (93.3%) of 15 patients with GA, 26 (92.9%) of 28 patients with GU, 22 (95.7%) of 23 patients with DU, and 6 (85.7%) of 7 patients with GU and DU (P = 0.84). Sequences of cagDE and vacA in our Japanese strains were highly homologous with one another, and there were no disease-specific mutations. CONCLUSIONS: Most of the H. pylori strains in Japan were cagDE-positive, vacA s1 type, regardless of clinical outcome. The present study also indicated that these genes were conserved well among our H. pylori isolates.