Yamaoka Y, Kodama T, Kita M, Imanishi J, Kashima K, Graham D Y
Department of Medicine, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas 77030, USA.
Helicobacter. 1998 Dec;3(4):241-53. doi: 10.1046/j.1523-5378.1998.08056.x.
Mosaicism in vacA alleles with three distinct families of vacA signal sequences (s1a, s1b and s2) and two distinct families of middle region alleles (m1 and m2) has been reported. It was suggested that the vacA s1a genotype was closely associated with duodenal ulcer disease and with high cytotoxin production. The aim of this study was to evaluate the role of vacA genotyping with respect to gastric inflammation and injury, cytotoxin activity, and clinical presentation.
H. pylori from patients with gastritis, peptic ulcer disease, or gastric cancer were characterized by vacA typing by polymerase chain reaction (PCR) and DNA sequencing. In vitro cytotoxin activity was assessed by vacuolation assay using Vero cells as well as with Hela cells.
Four hundred ninety-one strains were tested. vacA genotype s1a/m1 was present in more than 95% of strains independent of presentation with gastritis, peptic ulcer, or gastric cancer. No vacA genotype was associated with high average cytotoxin activity. The s2/m2 isolates had low or absent cytotoxin activity. All cagA negative strains (n = 18) were s1a strains and both s2/m2 strains were cagA positive. One strain that was a recombinant of m1 and m2 strains was identified and had low cytotoxin activity. The nucleotide and amino acid sequences between original m1 strains and Japanese m1 strains (new m1 strains) were about 85% and 81%, respectively. Strains with the new m1 genotype had nucleotide and amino acid sequences similarity of more than 96%. There was no difference in cytotoxin activity between strains with the Western type m1 and the new type m1 genotype.
In this as in other reported studies ( approximately 1500 patients overall) vacA genotype was strongly but not exclusively associated with the presence of cagA. Overall, the studies did not support a role for vacA genotyping in relation to cytotoxin activity, virulence, histologic finding, or risk of a particular H. pylori disease. vacA genotype s1 is likely to be a surrogate marker for the presence of the cag pathogenicity island.
已有报道称空泡毒素A（vacA）基因存在镶嵌现象，其具有三个不同的空泡毒素A信号序列家族（s1a、s1b和s2）以及两个不同的中间区域等位基因家族（m1和m2）。有人提出vacA s1a基因型与十二指肠溃疡病及高细胞毒素产生密切相关。本研究的目的是评估vacA基因分型在胃炎症和损伤、细胞毒素活性及临床表现方面的作用。
通过聚合酶链反应（PCR）和DNA测序对来自胃炎、消化性溃疡病或胃癌患者的幽门螺杆菌进行vacA分型。使用Vero细胞以及Hela细胞通过空泡形成试验评估体外细胞毒素活性。
共检测了491株菌株。无论表现为胃炎、消化性溃疡还是胃癌，超过95%的菌株存在vacA基因型s1a/m1。没有vacA基因型与高平均细胞毒素活性相关。s2/m2分离株的细胞毒素活性低或无活性。所有细胞毒素相关基因A（cagA）阴性菌株（n = 18）均为s1a菌株，且所有s2/m2菌株均为cagA阳性。鉴定出一株为m1和m2菌株重组体的菌株，其细胞毒素活性低。原始m1菌株与日本m1菌株（新m1菌株）之间的核苷酸和氨基酸序列分别约为85%和81%。具有新m1基因型的菌株的核苷酸和氨基酸序列相似性超过96%。西方型m1基因型菌株与新型m1基因型菌株之间的细胞毒素活性没有差异。
在本研究以及其他已报道的研究（总体约1500例患者）中，vacA基因型与cagA的存在密切相关，但并非唯一相关。总体而言，这些研究不支持vacA基因分型在细胞毒素活性、毒力、组织学发现或特定幽门螺杆菌疾病风险方面的作用。vacA基因型s1可能是细胞毒素相关基因致病性岛存在的替代标志物。
