Analysis of iceA genotypes in South African Helicobacter pylori strains and relationship to clinically significant disease

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Abstract
BACKGROUND South African Helicobacter pylori isolates are characterised by the universal presence ofcagA 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. AIM To characterise the genetic organisation and heterogeneity oficeA genotypes in different South African clinical isolates. PATIENTS AND METHODS 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 oficeA1 or iceA2genes, and for differences in the genetic organisation oficeA2 by polymerase chain reaction, Southern hybridisation analysis, and sequencing. RESULTS 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′) oficeA2 and marked differences in predicted protein secondary structure of the iceA2protein 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 withiceA1 isolates which were invariablyvacA s1/iceA1(p< 0.005 v gastritis). Isolates from PUD patients were distinguished by the structurally alterediceA2D variant (53%; pv gastritis) while theiceA2C variant distinguished isolates from patients with gastritis alone (67%; p< 0.005v PUD). CONCLUSION In this study, an association between iceA1 and GC was noted while differences in variants oficeA2 differentiated between PUD and gastritis alone. Combination analyses oficeA genotypes andvacA alleles supported these associations.