Helicobacter pylori (H. pylori) cytotoxin-associated gene A protein (CagA) is the first bacterial oncoprotein identified in human gastric cancer. The carboxy terminus (C-terminus) of CagA may undergo polymorphisms to give different types of EPIYA motifs, which may exist in single or combination form within the infected host. Sequence variations in the 3' region of the cagA impose a functional impact to the translated CagA protein. In this study, we characterize the diversity of the H. pylori CagA EPIYA types, their associations with their hosts' clinical status, and the potential of using the whole 3' region of cagA as a genetic marker for the identification of Iranian isolates from different geographic locations. H. pylori was detected in 71 out of 177 examined Iranian patients with different gastroduodenal disorders. Genotyping of the cagA variable EPIYA motif was screened by polymerase chain reaction and gene sequencing was performed for all the detected cagA positive isolates. Out of 44 cagA-positive isolates, there were EPIYA motifs of ABC (30 isolates), ABCC (4 isolates), ABCCC (1 isolate), mixed types (6 isolates) and new types (3 isolates). We termed the newly identified EPIYA segment as EPIYA- A-B/C. Sequence analysis also showed the presence of uncommon EPIYA-like motifs (EPIYT and QPIYP) in some isolates. It is postulated that EPIYA type conversion through the presence of different repetitive sequences give rise to these new strains. We also identified 3 sequence motifs which may be applied as genetic markers for Iranian strains. Furthermore, EPIYA types ABCC and EPIYA- A-B/C showed association with duodenitis and gastric cancer, respectively. Further study with a larger number of strains is necessary to confirm the proposed associations and the identified sequence motifs as genetic markers. In conclusion, our study demonstrates the dominancy of Western type cagA gene and the diversity of the CagA C-terminal region in the tested Iranian strains.
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