Clinical Relevance of the babA2 Genotype of Helicobacter pylori in Japanese Clinical Isolates

Abstract

Genotypic variation of Helicobacter pylori is speculated to associate with different clinical outcomes. In Western countries, the gene encoding blood group antigen-binding adhesin (BabA), babA2, is of high clinical relevance and is a useful marker to identify patients who are at higher risk for peptic ulceration and gastric adenocarcinoma, as are vacA and cagA. We investigated the presence of babA2 and cagA in 179 Japanese clinical isolates by PCR and Southern blot analysis and looked for correlations with various clinical outcomes (nonulcer dyspepsia, duodenal ulcers, gastric ulcers gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma). The prevalence of the babA2 genotype was 84.9% and that of the cagA genotype was 96.1%. There was no correlation between the babA2 and cagA genotypes, and there was no association between the babA2 or cagA status and clinical outcome. These results indicate that babA2 status is not of high clinical relevance in Japan and that Japanese strains are different from those infecting Western populations.Helicobacter pylori infection in the stomach activates a mucosal inflammatory response and leads to diverse clinical outcomes in humans (3). Most infected persons are asymptomatic with histologic gastritis (22), or they may develop a gastric or duodenal ulcer (1), adenocarcinoma (13), or mucosa-associated lymphoid tissue (MALT) lymphoma (27, 32) of the stomach.Numerous studies indicate that both bacterial and host factors may be important in leading to particular clinical and pathological sequelae of the infection. Among the bacterial factors, the role of the ability to adhere to epithelial cells is crucial in the initiation of a gastric inflammatory response (17,24,28). The blood group antigen-binding adhesin BabA has been shown to mediate adherence of H. pylori to human Lewis b (␣-1,3/4-difucosylated) blood group antigens on gastric epithelial cells (5). In vitro adherence assays revealed that H. pylori bound in a lineage-specific manner to gastric surface mucous cells mediated by fucosylated blood group antigens (11). Furthermore, a study using transgenic mice expressing the human Lewis b epitope in gastric epithelial cells indicated that Lewis b antigens function as receptors for an H. pylori adhesin and mediate its attachment to gastric pit and surface mucous cells (12). The attachment of H. pylori to gastric epithelial cells in such transgenic mice resulted in the development of chronic gastritis and gastric atrophy (15). In a recent study, the gene encoding BabA was cloned (and named babA2), thus allowing the identification of H. pylori strains harboring the babA2 genotype by PCR (18).The cag pathogenicity island is one of the major virulence factors of H. pylori, and there is a high frequency of the presence of the cagA gene in the cag pathogenicity island in patients with duodenal ulcers (16), atrophic gastritis (21, 22), gastric carcinomas (4), and MALT lymphomas (9) in Western countries. However, in Japan H. pylori strains harboring the cagA gene have not be...

Frecuencia de los genotipos babA2, oipA y cagE de Helicobacter pylori en pacientes colombianos con enfermedades gastroduodenales.

“…En Japón se reporta una prevalencia de babA2 mucho mayor (84,9%), QUIROGA A.J., CITTELLY D.M., BRAVO M.M. sin asociación significativa entre su presencia y el resultado clínico de la infección (37).…”

Roles of Helicobacter pylori BabA in gastroduodenal pathogenesis

“…Most previous studies evaluating BabA (babA) status have used PCR techniques based on detection of the 10 bp deletion to distinguish between the babA2 and babA1 genes ( Table 2) [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] . However, as described above, strains carrying the prototypical silent babA1 gene are very rare, and in addition, the BabA protein levels often do not match the presence of the babA (babA2) gene [31] .…”

Helicobacter pylori BabA Expression, Gastric Mucosal Injury, and Clinical Outcome

“…babA status (babA2 positive or negative) was determined by PCR using primer pairs and amplification conditions previously described (Figure 1). [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Most of these primers were designed to detect the 10-bp signal sequence deletion of babA1, which is absent in babA2. Most previous studies used primer pair A (babA2S and babA2AS) ( Table 1) in which 2 nucleotides of the forward primer were changed from the known sequences of the babA2 gene from strain CCUG17875 (ie, AC to GT) ( Figure 1).…”

“…24,25 Finally, not all of these PCR-based studies have shown an association between babA2 and intense cellular mucosal inflammations and/ or increased risk of peptic ulcer diseases and gastric cancer (Table 1). [10][11][12][13]19,20,22 Therefore, in the current study, we have compared results from PCR-based strategies that currently are used to predict BabA functional status with those from strategies that measure actual babA expression (ie, immunoblotting) and Le b binding.…”

“…3 Most studies evaluating BabA status have used polymerase chain reaction (PCR) techniques based on detection of the 10-bp deletion to distinguish between the babA2 and babA1 genes ( Table 1). [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] However, the ability of such PCR-based strategies to detect the presence of a functional babA gene is questionable. For example, H pylori strains unable to bind to Lewis b antigen (Le b ) have been reported to contain signal peptide sequences that are identical to those of strains with a functional babA2 gene (eg, strain 26695).…”