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. CagApositive strains are more likely to cause gastric cancer than CagA-negative strains. Based on EPIYA (GluPro-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.

Association between Helicobacter pylori Virulence Factors and Gastroduodenal Diseases in Okinawa, Japan

“…Recent studies have shown that Western-type cagA in Japan (J-Western type) was different from that of the typical Westerntype cagA found in Western countries (39). We also reported that J-Western cagA possesses a 12-bp insertion in the cagA sequence compared to typical Western cagA strains (32).…”

Prevalence of EPIYA motifs in Helicobacter pylori strains isolated from patients with gastroduodenal disorders in northern Iran

“…EPIYA-C and -D serve as the primary CagA phosphorylation sites and are required for binding to SHP-2 (12). Two different combinations of these motifs have been found in two distinct geographical locations, Western CagA and Eastern CagA (13). EPIYA-A and B are conserved in both two combinations (Western and Eastern), while EPIYA-C (up to 3 repeats) is specific for Western combination, and EPIYA-D is specific for Eastern strains (14).…”

J-Western Forms of Helicobacter pylori cagA Constitute a Distinct Phylogenetic Group with a Widespread Geographic Distribution

“…These studies have detected striking geographic differences in cagA sequences (26,36,53,60,63). For example, cagA sequences in H. pylori strains from East Asia or H. pylori strains from Amerindian persons within the Amazon are phylogenetically distinct from the cagA sequences that are commonly found in H. pylori strains from Western countries (26,34,36,53).…”

“…Interestingly, two different subtypes of cagA have been detected in Japan. One subtype (which encodes an EPIYA-D motif) closely resembles the cagA alleles found in other parts of East Asia, whereas a second subtype encodes an EPIYA-C motif, which is typically found in Western forms of CagA (26,60,63). The latter subtype has been termed a "Japanese subtype of Western CagA" and has been designated "J-Western" (26,60).…”

“…Nearly all of the J-Western cagA alleles described in the literature have been detected in H. pylori strains from Okinawa, Japan, and there has been very little study of this cagA group (14,24,26,60). One hypothesis is that J-Western forms of cagA arose recently, possibly related to the presence of American troops in Okinawa at the end of World War II (26).…”