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 cytotoxin gene (vacA) alleles which correlate with clinically significant disease. However, the candidate virulence marker gene iceA has not been investigated.


OBJECTIVE
To characterise the genetic organisation and heterogeneity of iceA genotypes in different South African clinical isolates.


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 of iceA1 or iceA2 genes, and for differences in the genetic organisation of iceA2 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') 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).


CONCLUSIONS
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.
Kidd
M
M
GI Clinic and Department of Medicine, University of Cape Town and Groote Schuur Hospital, South Africa.
Peek
R M
RM
Lastovica
A J
AJ
Israel
D A
DA
Kummer
A F
AF
Louw
J A
JA
D000230:Adenocarcinoma / Q000382:microbiology; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics; D015139:Blotting, Southern; D005756:Gastritis / Q000382:microbiology; D005798:Genes, Bacterial / Q000235:genetics*; D018740:Genetic Heterogeneity; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D010437:Peptic Ulcer / Q000382:microbiology; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000382:microbiology; D014774:Virulence / Q000235:genetics
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C074689:VacA protein, Helicobacter pylori; C063113:ice nucleation protein