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     

cagA基因与细胞因子在幽门螺杆菌致病中的作用

近来发现部分幽门螺杆菌（Ｈｐ）菌株能表达细胞空泡毒素（ｖａｃＡ）和细胞空泡毒素相关蛋白（ｃａｇＡ）。我们应用聚合酶链反应（ＰＣＲ）技术检测ＨｐｃａｇＡ基因，对Ｈｐ进行基因分型，并检测胃黏膜孵育上清中白细胞介素（ＩＬ）８、ＩＬ６、肿瘤坏死因子α（...     

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。     

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     

幽门螺杆菌vacA基因型和cagA基因及其表达产物

幽门螺杆菌（Ｈｐ）的ｖａｃＡ基因和ｃａｇＡ基因分别表达ＶａｃＡ和ＣａｇＡ蛋白两种毒力因子。两种毒力因子之间有着相互的关联，在Ｈｐ引起的胃肠疾病中具有重要作用，Ｈｐ感染的临床发病与Ｈｐ的ｖａｃＡ基因型，具有ｃａｇＡ基因Ｈｐ以及ＶａｃＡ和ＣａｇＡ蛋白的表达有着密切的关系。     

消化性溃疡及胃癌患者血清CagA VacA抗体研究

细胞毒素相关蛋白（ｃｙｔｏｔｏｘｉｎａｓｓｏｃｉａｔｅｄｐｒｏｔｅｉｎ，ＣａｇＡ）和空泡形成毒素（ｖａｃｕｏｌａｔｉｎｇｃｙｔｏｔｏｘｉｎ，ＶａｃＡ）是幽门螺杆菌（Ｈｐ）相应的ＣａｇＡ，ＶａｃＡ基因编码产生的两种蛋白质，是Ｈｐ的重要致病因子，也作为Ｈｐ毒力分型的标志［１］，与消化性溃疡（ＰＵ）、胃癌有密切关系［２，３］，由于Ｈｐ菌株类型的分布存在明显的地区差异［４，５］．我们检测了本地区ＰＵ和胃癌患者的血清ＣａｇＡ，ＶａｃＡ抗体，旨在探讨我国东南沿海地区ＣａｇＡ，ＶａｃＡ与ＰＵ及胃癌的关系．１　…     

江苏省胃癌高发区幽门螺杆菌感染与胃癌、基因突变之间的关系

目的研究江苏省胃癌高发区幽门螺杆菌（Ｈｐ）感染及其毒力因子与胃癌、基因突变之间的关系。方法用酶链免疫吸附测定（ＥＬＩＳＡ）、免疫印迹及聚合酶链反应单链构象多态性分析（ＰＣＲＳＳＣＰ）等方法,分析了５０例胃癌及５０例配对胃炎患者的Ｈｐ感染、Ｈｐ的细胞毒素相关蛋白（ＣａｇＡ）、空泡细胞毒素（ＶａｃＡ）情况及胃粘膜ｐ５３基因第５～８外显子的突变。结果胃癌组中Ｈｐ阳性率及ＣａｇＡ阳性率均显著高于胃炎组,ｐ５３基因突变与Ｈｐ感染有非常显著的相关性,而与ＣａｇＡ、ＶａｃＡ的表达无关。结论Ｈｐ（尤其是ＣａｇＡ阳性菌株）感染能增加胃癌的发病风险,在Ｈｐ致癌过程中ｐ５３等基因突变可能起了关键的作用,研究结果为根治Ｈｐ以预防胃癌发生提供了实验依据。     

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     

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。     

Virulence and potential pathogenicity of coccoid Helicobacter pylori induced by antibiotics

AIM: To explore the virulence and the potential pathogenicity of coccoid Helicobacter pylori (H. pylori) transformed from spiral form by exposure to antibiotic. METHODS: Three strains of H. pylori, isolated from gastric biopsy specimens of confirmed peptic ulcer, were converted from spiral into coccoid from by exposure to metronidazole. Both spiral and coccoid form of H. pylori were tested for the urease activity, the adherence to Hep-2 cells and the vacuolating cytotoxicity to Hela cells, and the differences of the protein were analysed by SDS-PAGE and Western blot. The mutation of the genes including ureA, ureB,hpaA, vacA and cagA, related with virulence, was detected by means of PCR and PCR-SSCP. RESULTS: In the coccoid H. pylori,the urease activity, the adherence to Hep-2 cells and the vacuolating cytotoxicity to Hela cells all decreased. In strain F44, the rate and index of adherence reduced from 70.0% +/- 5.3% to 33% +/- 5.1% and from 2.6 +/- 0.4 to 0.96 +/- 0.3 (P < 0.01), respectively. The invasion of coccoid H. pylori into Hep-2 cell could be seen under electronmicroscope. SDS-PAGE showed that the content of the protein with the molecular weight over Mr 74000 decreased, and the hybriditional signal in band M(r) 125000 weakened, while the band M(r)110000 and M(r)63000 strengthened in coccoid H.pylori as shown in Western blot. The results of PCR were all positive, and PCR-SSCP indicated that there may exist the point mutation in gene hpaA or vacA. CONCLUSION: The virulence and the proteins with molecular weight over M(r)74000 in coccoid H.pylori decrease, but no deletion exists in amplification fragments from ureA, ureB, hpaA, vacA and cagA genes, suggesting that coccoid H.pylori may have potential pathogenicity.     

Cloning and sequencing of cagA gene fragment of Helicobacter pylori with coccoid form

AIM: To clone and sequence the cagA gene fragment of Helicobacter pylori (H pylori) with coccoid form. METHODS: H pylori strain NCTC11637 were transformed to coccoid form by exposure to antibiotics in subinhibitory concentrations. The coccoid H pylori was collected. cagA gene of the coccoid H pylori strain was amplified by PCR. After purified, the target fragment was cloned into plasmid pMD-18T. The recombinant plasmid pMD-18T-cagA was transformed into E.coli JM109. Positive clones were screened and identified by PCR and digestion with restriction endonucleases. The sequence of inserted fragment was then analysed. RESULTS: cagA gene of 3,444 bp was obtained from the coccoid H pylori genome DNA. The recombinant plasmid pMD-18T-cagA was constructed, then it was digested by BamH I+Sac I, and the product of digestion was identical with the predicted one. Sequence analysis showed that the homology of coccoid and the reported original sequence H pylori was 99.7%. CONCLUSION: The recombinant plasmid containing cagA gene from coccoid H pylori has been constructed successfully. The coccoid H pylori contain completed cagA gene, which may be related to pathogenicity of them.     

Significance of cagA status and vacA subtypes of Helicobacter pylori in determining gastric histopathology: virulence markers of H. pylori and histopathology

BACKGROUND: It has been suggested that Helicobacter pylori strains containing the cytotoxin-associated gene A (cagA), and s1m1 genotype of vacuolating cytotoxin gene A (vacA) may have been associated with peptic ulcer disease. The aim of the present study was to analyze such an association of cagA presence and vacA subtypes of H. pylori with histopathological findings in patients with gastritis. METHODS: Sixty-five independent H. pylori strains isolated from Turkish patients with gastritis were analyzed. The antral biopsy specimens were processed for culture and histopathology. Histopathological features were recorded and graded according to updated Sydney system. The vacA subtypes and cagA gene were tested by polymerase chain reaction. RESULTS: Mild degree of antral density was associated with mild degree of gastric neutrophil infiltration (P = 0.010). Positive cagA status correlated significantly with the presence of atrophy (P = 0.035) and neutrophil infiltration (P < 0.001), but not with H. pylori density (P = 0.754) nor the degree of mononuclear cell infiltration (P = 0.945). The vacA subtypes were independent of gastric histopathology. The odds ratios for atrophy and neutrophil infiltration of cagA+ versus cagA- strains were 3.62 (95% confidence interval [CI]: 1.04-12.66) and 53.18 (95%CI: 11.08-255.23), respectively. CONCLUSION: The presence of the cagA gene is strongly associated with atrophic and active gastritis. Distinct vacA subtypes of H. pylori appear to have no association with histopathological findings of gastritis.     

Cloning and sequencing of cagA gene fragment of Helicobacter pylori with coccoid form

AIM:To clone and sequence the cagA gene fragment ofHelicobacter pylori(H pylon)with coccoid form.METHODS:Hpyloristrain NCTC11637 were transformedto coccoid form by exposure to antibiotics in subinhibitoryconcentrations.The coccoid Hpyloriwas collected,cagAgene of the coccoid Hpyloristrain was amplified by PCR.After purified,the target fragment was cloned into plasmidpMD-18T.The recombinant plasmid pMD-18T-cagA wastransformed into E.coli JM109.Positive clones were screenedand identified by PCR and digestion with restrictionendonucleases.The sequence of inserted fragment wasthen analysed.RESULTS:cagA gene of 3 444 bp was obtained from thecoccoid Hpylori genome DNA.The recombinant plasmidpMD-18T-cagA was constructed,then it was digested byBamH I Sac I,and the product of digestion was identicalwith the predicted one.Sequence analysis showed that thehomology of coccoid and the reported original sequenceH pylori was 99.7%.CONCLUSION:The recombinant plasmid containing cagAgene from coccoid H pylorihas been constructed successfully.The coccoid H pylori contain completed cagA gene,whichmay be related to pathogenicity of them.     

Conservation of the cag pathogenicity island is associated with vacA alleles and gastroduodenal disease in South African Helicobacter pylori isolates

BACKGROUND: The development of clinically significant disease in South Africa is associated with the vacuolating cytotoxin gene (vacA) s1 genotype but not with the presence of the cytotoxin associated gene cagA. cagA occurs in >95% of South African isolates and is a variable marker for the entire cag pathogenicity island (PAI). AIM: To characterise the cagPAI in South African isolates and to investigate if structural variants of this multigene locus were associated with variations in vacA status and clinical outcome. PATIENTS AND METHODS: We studied 109 Helicobacter pylori strains (36 from patients with peptic ulceration, 26 with gastric adenocarcinoma, and 47 with no pathology other than gastritis) for differences in selected genes of the cagPAI and alleles of vacA by polymerase chain reaction. RESULTS: All strains were cagA(+). Sixty five (60%) strains had an intact contiguous cagPAI; 78% of peptic ulcer isolates, 73% of gastric adenocarcinoma isolates, but only 40% of gastritis alone isolates (p< 0.01). The entire cagII region was undetectable in 23% of gastritis alone isolates but in only 8% of peptic ulceration isolates (p<0.05). The vacA signal sequence and mid region demonstrated a strong relationship between the virulence associated vacA s1 (p<0.005) and vacA m1 (p=0.05) alleles and an intact cagPAI. CONCLUSION: Although a complete cagPAI was a feature of most infected individuals, deletions in the 5' region of this genetic locus were associated with gastritis alone and with the non-cytotoxic s2/m2 vacA genotype.     

Genetic analysis and clinical evaluation of vacuolating cytotoxin gene A and cytotoxin-associated gene A in Taiwanese Helicobacter pylori isolates from peptic ulcer patients

The aims of this study were to investigate the cytotoxin-associated gene A (cagA) and vacuolating cytotoxin gene A (vacA) subtype in Taiwanese H. pylori isolates from patients with gastroduodenal diseases and to assess the relationship between genotypes of isolates and clinical features. The vacA s1a allele was found in all isolates and vacA m1 allele was found in 15% of isolates. The cagA gene was found in 82.5% of isolates. The vacA s1a/m2 strains had a significantly higher prevalence rate than vacA s1a/m1 strains in Taiwan (p < 0.05). By aligning and comparing the nucleotide and amino acid sequences of vacA from the Taiwanese isolates, the signal sequence and N-terminal region were found to be highly conserved, but the middle region was found to be highly heterogeneous. Determining the relationship between the genotypes and clinical features, we found that the cagA gene was more closely associated with duodenal ulcer than with gastric ulcer and the vacA s1a/m2 strain was more closely associated with active chronic gastritis and atrophic gastritis than with chronic gastritis. Together, our results indicated that (i) the middle region of vacA gene in Taiwanese isolates was heterogeneous; (ii) s1a/m2 vacA strains had a high prevalence in Taiwanese peptic ulcers; and (iii) the cagA gene was significantly associated with duodenal ulcer.     

Helicobacter pylori vacA genotypes and cagA gene in a series of 383 H. pylori-positive patients

BACKGROUND: Only 10-15% of all patients infected with Helicobacter pylori develop peptic ulcer disease (PUD) or gastric cancer. Apart from immunological factors in the host, virulence determinants of H. pylori such as the vacuolating cytotoxin (VacA) or the cytotoxin-associated protein A (CagA) might represent a predisposition for the development of PUD. METHODS: We studied antral biopsies of 383 H. pylori-positive patients with peptic ulcer disease (PUD) or other H. pylori-related diseases for H. pylori vacA genotypes and the presence of the cagA gene by PCR. RESULTS: VacA genotypes and cagA status could be completely determined in 357 (93.2%) of the patients. In 91 (93.8%) of 97 patients with PUD, the vacA s1 genotype (s1m1, 45; s1m2, 46 patients) was present. The vacA s2m2 genotype was found in only 6 (6.2%) of 97 patients with PUD. In contrast, 180 (75.3%) of 239 patients (s1m1, 89; s1m2, 91 patients) without PUD and without gastric malignancies harbored strains with the vacA s1 genotype. The vacA genotype s2m2 was found in 59 (24.7%) of these patients. The presence of the cagA gene was closely associated with the vacA genotype s1 and found in 124 (88.6%) and in 113 (80.7%) of patients with the s1m1 or s1m2 genotypes, respectively, whereas strains with the genotype s2m2 were almost exclusively cagA negative. CONCLUSION: Most H. pylori strains found in patients with PUD possess the vacA s1 genotype and the cagA gene. Patients with this type of H. pylori strain but without PUD might be at higher risk of developing PUD. In contrast, the risk for PUD might be significantly decreased in those patients who are infected by H. pylori strains with the vacA s2 genotype lacking the cagA gene.     

Helicobacter pylori vacA genotypes and cagA status and their relationship to associated diseases

Helicobacter pylori (H. pylori ) is a major causativebacterium of chronic gastritis, peptic ulcer and mucosaassociated lymphoid tissue lymphoma in humans, and associated with an increased risk of gastric cancer[1 -8]. An important virulant factor of H. pylori is the vacuolating cytotoxin ( VacA ) encoded by vacA that induces cytoplasmic vacuolation in target cells both in vitro and in vivo[9-11]. VacA is produced as a 140 kDa precursor which contains an N-terminal signal peptide and an approximately 33 kDa C-terminal outer membrance exporter. The precursor is cleaved at both N-terminal and C-terminal and secreted into the extracellular milieu as a 95 kDa mature protein. The mature protein futher undergoes specific cleavage to yield 37 kDa and 58 kDa subunits[12-14] Although vacA is present in all H. pylori strains, only about 50% to 60% of strains can induce vacuolation of epithelial cells as assessed by the HeLa cell assay. vacA shows considerable genetic variation in H. pylori isolated from all over the world and contains at least two variable regions. The s region exists as sl or s2 allelic types. Among type sl strains, subtypes sla and slb have been identified. The m region occurs as ml or m2 allelic types. Specific vacA genotype of H. pylori strains are associated with the production of the cytotoxin in vitro, epithelial damage in vivo, and clinical consequences[15-27]. The other virulant factor is the cytotoxin-associated protein (CagA) encoded by the cytotoxin-associated gene (cagA). The cagA gene is present in about 60% to 70% of strains and all of these strains express the cagA. The presence of cagA is also associated with the production of the cytotoxin in vitro, and clinical outcome[24-30]. The aim of this study was (i) to identify vacA genotypes and cagA status of H. pylori isolated from Chinese patients; (ii) to evaluation the relatioship beween vacA genotypes, cagA status and related gastroenterological disorders.     

Prevalence of vacA, cagA and babA2 genes in Cuban Helicobacter pylori isolates

AIM： To investigate the prevalence of vacuolating cytotoxin （vacA）, cytotoxin associated gene A （cagA） and blood adhesion binding antigen （babA2） genotypes of Helicobacter pylori （H pylori） isolates from Cuban dyspeptic patients. METHODS： DNA was extracted from Hpylori-positive cultures taken from 130 dyspeptic patients. Genotyping was performed by PCR, using specific primers for vacA （s1, s2, m1, m2）, cagA and babA2 genes. Endoscopic observations and histological examinations were used to determine patient pathologies. RESULTS： vacA alleles s1, s2, m1 and m2 were detected in 96 （73.8%）, 34 （26.2%）, 75 （57.7%） and 52 isolates （40%）, respectively, while the cagA gene was detected in 95 isolates （73.2%）. One hundred and seven isolates （82.3%） were babA2-positive. A significant correlation was observed between vacAs1m1 and cagA and between vacAs1ml and babA2 genotypes （P 〈 0.001 and P 〈 0.05, respectively） and between babA2 genotype and cagA status （P 〈 0.05）; but, no correlation was observed between vacAsl and babA2 genotypes. Eighty five （65.4%） and 73 （56.2%） strains were type 1 （vacAsl-cagA-positive） and ＂triplepositive＂ （vacAs1-cagA-babA2-positive）, respectively, and their presence was significantly associated with duodenal ulcer （P 〈 0.01 and P 〈 0.001, respectively）. CONCLUSION： The distribution of the main virulence factors in the Cuban strains in this study resembled that of the Western-type strains, and the more virulent H pylori isolates were significantly associated with duodenal ulcer, ulcer disease being the worst pathology observed in the group studied.     

Relation between vacA subtypes, cytotoxin activity, and disease in Helicobacter pylori-infected patients from the netherlands

OBJECTIVE: The vacuolating cytotoxin of Helicobacter pylori (H. pylori) is encoded by vacA, of which allelic variation has been described. In the U.S., H. pylori strains with the signal sequence allele s1a are associated with enhanced gastric inflammation and with peptic ulcer disease (PUD). The m1 middle region allele is linked with more severe gastric epithelial damage. However, the distribution of H. pylori genotypes and the association with disease may be different in other geographical areas. The aim of this study was to establish whether vacA types among H. pylori isolates from Dutch patients are associated with disease. METHODS: The cytotoxin activity of the H. pylori isolates from 34 PUD patients and 46 patients with functional dyspepsia (FD) was assessed by an in vitro assay using HeLa cells as indicator cells. The vacA types and cagA status of the isolates were assessed by polymerase chain reaction (PCR). RESULTS: vacA s1-type H. pylori displayed cytotoxin activity more frequently than s2 vacA-type H. pylori (p = 0.003). This difference was not significant when only cagA+ H. pylori were considered. H. pylori isolates with the m1 vacA type exhibited a higher cytotoxin activity, independent of cagA (p = 0.006). Ninety-four percent (32/34) of the PUD patients and 74% (34/46) of the FD patients were infected with s1 vacA-type H. pylori (p = 0.04). When only cagA+ H. pylori were considered, s1 vacA type was not associated with disease. In addition, neither the s1a nor s1b subtypes correlated with disease. CONCLUSIONS: An association between vacA subtypes and disease could not be established in this patient population, due to the strong linkage between vacA s1 type and cagA.