VARIANTS OF THE 3' REGION OF THE CAGA GENE IN HELICOBACTER-PYLORI ISOLATES FROM PATIENTS WITH DIFFERENT HELICOBACTER-PYLORI-ASSOCIATED DISEASES

The CagA protein of Helicobacter pylori is an immunogenic antigen of v ariable size and unknown function that has been associated with increa sed virulence as well as two mutually exclusive diseases, duodenal ulc er and gastric carcinoma. The 3' region of the cagA gene contains repe ated sequences. To determine whether there are structural changes in t he 3' region of cagA that predict outcome of H. pylori infection, we e xamined 155 cagA gene-positive H. pylori isolates from Japanese patien ts including 50 patients with simple gastritis, 40 with gastric ulcer, 35 with duodenal ulcer, and 30 with gastric cancer. The 3' region of the cagA gene was amplified by PCR followed by sequencing. CagA protei ns were detected by immunoblotting using a polyclonal antibody against recombinant CagA. One hundred forty-five strains yielded PCR products of 642 to 651 bp; 10 strains had products of 756 to 813 bp. The seque nce of the 3' region of the cagA gene in Japan differs markedly from t he primary sequence of cagA genes from Western isolates. Sequence anal ysis of the PCR products showed four types of primary gene structure ( designated types A, B, C, and D) depending on the type and number of r epeats. Six of the seven type C strains were found in patients with ga stric cancer (P < 0.01 in comparison to noncancer patients). Compariso n of type A and type C strains from patients with gastric cancer showe d that type C was associated with higher levels of CagA antibody and m ore severe degrees of atrophy. Differences in cagA genotype may be use ful for molecular epidemiology and may provide a marker for difference s in virulence among cagA-positive H. pylori strains.