Diverse characteristics of the CagA gene of Helicobacter pylori strains collected from patients from southern vietnam with gastric cancer and peptic ulcer

Abstract

The pathogenesis of gastroduodenal diseases is related to the diversity of Helicobacter pylori strains. CagA-positive strains are more likely to cause gastric cancer than CagA-negative strains. Based on EPIYA (Glu-Pro-Ile-Tyr-Ala) motifs at the carboxyl terminus corresponding to phosphorylation sites, H. pylori CagA is divided into East Asian CagA and Western CagA. The former type prevails in East Asia and is more closely associated with gastric cancer. The present study used full sequences of the cagA gene and CagA protein of 22 H. pylori strains in gastric cancer and peptic ulcer patients from Southern Vietnam to make a comparison of genetic homology among Vietnamese strains and between them and other strains in East Asia. A phylogenetic tree was constructed based on full amino acid sequences of 22 Vietnamese strains in accordance with 54 references from around the world. The cagA gene was found in all Vietnamese H. pylori strains. Twenty-one of 22 (95.5%) strains belonged to the East Asian type and had similar characteristics of amino acid sequence at the carboxyl terminus to other strains from the East Asian region. From evidence of East Asian CagA and epidemiologic cancerous lesions in Vietnam, H. pylori-infected Vietnamese can be classified into a high-risk group for gastric cancer, but further studies on the interaction among environmental and virulence factors should be done. Finally, phylogenetic data support that there is a Japanese subtype in the Western CagA type.

FIG. 1.

Alignment of the deduced amino acid sequence of the carboxy terminus of CagA in 22 H. pylori strains from Southern Vietnam, the representative Western strain 26695 (accession no. AE000569), and the Japanese strain F32 (accession no. AF202972). (a) Amino acid sequences in strains 26695, VN7 (EPIYA-ABD), VN28 (EPIYA-ABCC), and F32. (b) Eighteen Vietnamese strains had the EPIYA-ABD motif, strain F32 had the EPIYA-ABD motif, strain VN4 had the EPIYA-AB′D motif, strainVN14 had the EPIYA-AB″D motif, and VN16 had the EPIYA-AABD motif. The well-conserved region between motifs EPIYA-B and EPIYA-D is indicated by a double underline, and the completely conserved region is indicated by underlined letters. Strains VN20 and VN16 have marked diversity in amino acid sequence between EPIYA-B and EPIYA-D in comparison to other strains. In the EPIYA-D region, 8 of 21 (38.1%) strains have an additional residue, a glutamine (E), upstream of the EPIYA-D motif (indicated by single underlines).

FIG. 2.

A phylogenetic tree constructed based on the complete amino acid sequence of H. pylori CagA protein in 22 isolates from Southern Vietnam (VietnamHP no. 7, 6, 17, 16, 4, 23, 27, 33, 2, 5, 15, 31, 24, 25, 20, 3, 8, 36, 22, 14, 32, 28 [given in the order shown in Tables 2 and 3]) compared with complete amino acid sequence of H. pylori CagA protein in 54 isolates from the GenBank database, including Japan (32 strains, 14 with the Western CagA type from Okinawa and 18 with the East Asian CagA type from Fukui), China (5 strains), India (2 strains), Australia (4 strains), Europe (4 strains), and America (7 strains). The length of the horizontal bar indicates the number of amino acid substitutions per site.