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

Background-South African Helicobacter pylori isolates are characterised by the universal presence of cagA but have differences in vacuolating cytotoxi n 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 of iceA geno types 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 adeno carcinoma (GC), and 37 with non-erosive gastritis) for the presence of iceA 1 or iceA2 genes, and for differences in the genetic organisation of iceA2 by polymerase chain reaction, Southern hybridisation analysis, and sequenci ng. Results-Genetic analysis of iceA1 demonstrated significant homology (92-95% ) with the USA type strain 26695 and probably functions as a transcriptiona l regulator, while a novel variant (iceA2D') of iceA2 and marked difference s in predicted protein secondary structure of the iceA2 protein were define d. iceA1 was detected in 68% and iceA2 in 80% of all clinical isolates. Alt hough approximately 40% of patients had both strains, a higher prevalence ( p < 0.01) of GC patients were infected with iceA1 isolates which were invar iably vacA s1/iceA1 (p < 0.005 v gastritis). Isolates from PUD patients wer e distinguished by the structurally altered iceA2D variant (53%; p < 0.03 v gastritis) while the iceA2C variant distinguished isolates from patients w ith gastritis alone (67%; p < 0.005 v PUD). Conclusion-In this study, an association between iceA1 and GC was noted whi le differences in variants of iceA2 differentiated between PUD and gastriti s alone. Combination analyses of iceA genotypes and vacA alleles supported these associations.