Failure to confirm association of vac A gene mosaicism with duodenal ulcer disease

Failure to confirm association of vac A gene mosaicism with duodenal ulcer disease
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DOI:
10.1080/00365529850166842
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发表时间:
1998-02-01
影响因子:
1.9
通讯作者:
Graham, DY
Graham, DY
中科院分区:
医学4区
文献类型:
--
作者:
Go, MF;Cissell, L;Graham, DY

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背景:幽门螺杆菌vac A基因的嵌合体包括信号序列区(s1, s2)和中间区域(m1, m2)的两个等位基因变异家族,初步研究表明消化性溃疡疾病与vac A的s1亚型相关。我们比较了从十二指肠溃疡(DU)患者和单纯性胃炎受试者中分离的幽门螺杆菌不同vac A基因型的患病率。对s1型分离株进行进一步检测,以确定特定的vac as1 (s1a与s1b)基因型是否能够预测胃十二指肠疾病。方法:从德克萨斯州休斯顿的38例经内镜检查的DU患者和39例无症状幽门螺杆菌胃炎患者中分离出幽门螺杆菌。每个分离物的vac A基因型通过PCR扩增vac A基因特定区域的基因组DNA来确定。对s1 vac A亚型的分离株进行进一步检测,以确定它们是否具有s1a或s1b嵌合。结果:从十二指肠溃疡和无症状幽门螺杆菌胃炎患者中分离的s1基因型的频率无差异(分别为84%和79%,P = 0.77)。在16例十二指肠溃疡患者和15例幽门螺杆菌胃炎患者中检测到s1/m1 vac A基因型(P = 0.82)。对s1区域的详细分析未能显示s1a或s1b与十二指肠溃疡的相关性。24株菌株检测到s1a和s1b基因型,16株菌株检测到mi和m2中基因PCR扩增。结论:我们无法使用幽门螺杆菌vaca基因分型来预测患者样本中胃十二指肠疾病的类型。这种未能证实vac A基因型与十二指肠溃疡疾病的关联的结果与来自其他地区的样本不同。这很可能代表了幽门螺杆菌菌株在不同地理区域感染宿主种群的差异。这项研究证实了在得出存在疾病相关关联的结论之前,与广泛分离的地理区域的分离物建立统计关联的重要性。
Background: Mosaicism of the Helicobacter pylori vac A gene comprises two families of allelic variations of the signal sequence region (s1, s2) and of the mid-region (m1, m2), Initial studies suggested that peptic ulcer disease correlated with the s1 subtype of vac A. We compared the prevalence of various vac A genotypes of H. pylori isolates obtained from duodenal ulcer (DU) patients and subjects with simple gastritis. Those isolates with s1 type were further examined to determine whether the specific vac A s1 (s1a versus s1b) genotype enabled prediction of gastroduodenal disease. Methods: H. pylori isolates were obtained from 38 patient with endoscopically documented DU and 39 individuals with asymptomatic H. pylori gastritis from Houston, Texas. The vac A genotype of each isolate was determined by polymerase chain reaction (PCR) amplification of genomic DNA for specific regions of the vac A gene. Those isolates with s1 vac A subtype were further examined to determine whether they had s1a or s1b mosaicism. Results: There was no difference in frequency of the s1 genotype of isolates obtained from patients with duodenal ulcer or asymptomatic H. pylori gastritis in this sample (84% versus 79%, respectively; P = 0.77). The s1/m1 vac A genotype was detected in isolates from 16 duodenal ulcer patients versus 15 with H. pylori gastritis (P = 0.82). Detailed analysis of the s1 region failed to show a correlation of either s1a or s1b with duodenal ulcer. Both s1a and s1b genotypes were detected in 24 strains, and both mi and m2 mid-gene PCR amplicons were seen in 16 strains. Conclusions: We were unable to use H. pylori vac A genotyping to predict type of gastroduodenal disease in our patient sample. This failure to confirm an association of vac A genotype and duodenal ulcer disease differs from samples from other regions. This most likely represents an example of differences in H. pylori strains infecting host populations in different geographic regions. This study confirms the importance of establishing statistical associations with isolates from widely separate geographic regions before concluding that disease-related associations exist.