Kidd M, Peek R M, Lastovica A J, Israel D A, Kummer A F, Louw J A
GI Clinic and Department of Medicine, University of Cape Town and Groote Schuur Hospital, South Africa.
Gut. 2001 Nov;49(5):629-35. doi: 10.1136/gut.49.5.629.
South African Helicobacter pylori isolates are characterised by the universal presence of cagA but have differences in vacuolating cytotoxin gene (vacA) alleles which correlate with clinically significant disease. However, the candidate virulence marker gene iceA has not been investigated.
To characterise the genetic organisation and heterogeneity of iceA genotypes in different South African clinical isolates.
We studied H pylori strains isolated from 86 dyspeptic patients (30 with peptic ulcer disease (PUD), 19 with distal gastric adenocarcinoma (GC), and 37 with non-erosive gastritis) for the presence of iceA1 or iceA2 genes, and for differences in the genetic organisation of iceA2 by polymerase chain reaction, Southern hybridisation analysis, and sequencing.
Genetic analysis of iceA1 demonstrated significant homology (92-95%) with the USA type strain 26695 and probably functions as a transcriptional regulator, while a novel variant (iceA2D') of iceA2 and marked differences in predicted protein secondary structure of the iceA2 protein were defined. iceA1 was detected in 68% and iceA2 in 80% of all clinical isolates. Although approximately 40% of patients had both strains, a higher prevalence (p< 0.01) of GC patients were infected with iceA1 isolates which were invariably vacA s1/iceA1 (p< 0.005 v gastritis). Isolates from PUD patients were distinguished by the structurally altered iceA2D variant (53%; p<0.03 v gastritis) while the iceA2C variant distinguished isolates from patients with gastritis alone (67%; p< 0.005 v PUD).
In this study, an association between iceA1 and GC was noted while differences in variants of iceA2 differentiated between PUD and gastritis alone. Combination analyses of iceA genotypes and vacA alleles supported these associations.
南非幽门螺杆菌分离株的特征是普遍存在cagA，但空泡毒素基因（vacA）等位基因存在差异，这些差异与具有临床意义的疾病相关。然而，候选毒力标记基因iceA尚未得到研究。
对不同南非临床分离株中iceA基因型的遗传结构和异质性进行特征分析。
我们研究了从86例消化不良患者（30例患有消化性溃疡病（PUD），19例患有远端胃癌（GC），37例患有非糜烂性胃炎）中分离出的幽门螺杆菌菌株，通过聚合酶链反应、Southern杂交分析和测序检测iceA1或iceA2基因的存在以及iceA2遗传结构的差异。
iceA1的遗传分析显示与美国标准菌株26695具有显著同源性（92 - 95%），可能作为转录调节因子发挥作用，同时定义了iceA2的一个新变体（iceA2D'）以及iceA2蛋白预测二级结构的显著差异。在所有临床分离株中，68%检测到iceA1，80%检测到iceA2。虽然约40%的患者同时感染了这两种菌株，但GC患者中iceA1分离株的感染率更高（p < 0.01），这些分离株均为vacA s1/iceA1（与胃炎相比，p < 0.005）。PUD患者的分离株以结构改变的iceA2D变体为特征（53%；与胃炎相比，p < 0.03），而iceA2C变体则区分了仅患有胃炎患者的分离株（67%；与PUD相比，p < 0.005）。
在本研究中，发现iceA1与GC之间存在关联，而iceA2变体的差异区分了PUD和单纯性胃炎患者。iceA基因型和vacA等位基因的联合分析支持了这些关联。
