Gastric cancer arises through steps related to the presence of a chronic Helicobacter pylori infection, which leads to the precursor lesion, atrophic gastritis. The progression of gastric mucosal atrophy varies within and between different populations; and the differences relate to differences in H. pylori virulence, host genetic factors, and/or environmental factors. The important H. pylori virulence factors and host genetic factors are related to an increased inflammatory response and include the presence of the cag pathogenicity island, polymorphisms of host inflammationrelated cytokines (5, 6), drug metabolism-related enzymes (19,22), and growth factors (5,6,12,19,22,30).The vacuolating cytotoxin (VacA) was one of the first putative virulence factors discovered in H. pylori (4). Virtually all H. pylori strains possess a vacA gene; however, the in vitro vacuolating activities for cell lines vary considerably among strains; and the differences in the vacuolating activities are related to differences in the vacA structures at the signal (s) region (s1 and s2) and the middle (m) region (m1 and m2) (1). The s region encodes part of the signal peptide and the N terminus of the mature protein, whereas the m region encodes part of the 55,000-Da (55K) C-terminal subunit. The amount of toxin produced also varies according to the vacA m-region genotypes: vacA s1-m1 strains induce greater vacuolating activity than vacA s1-m2 strains (1, 11).Recently, a third polymorphic determinant of vacuolating activity was described as being located between the s and m regions and was termed the intermediate (i) region (16). Two i-region subtypes were described: the i1 and i2 subtypes. Among Western strains, vacA s1-m2 strains were noted to vary in their i-region genotypes; vacA s1-m1 and s2-m2 strains were exclusively i1 and i2, respectively. The vacA s1-i1-m2 strains induced vacuolation in rabbit kidney RK13 cells, whereas s1-i2-m2 strains did not. Clinically, the prevalence of the vacA i1 genotype in patients with gastric cancer was 80%, which was significantly higher than that in patients in an Iranian population with nonulcer dyspepsia (37%) (16). Subsequent studies showed that infection with vacA i1 strains was associated with gastric cancer in patients in Iranian and Italian populations and gastric ulcer in patients in Iraqi and Italian populations (2,8,16). This allowed the conclusion that the vacA i-region genotype might be a better predictor of the carcinogenic potential of H. pylori than the previously used vacA s-and mregion genotypes. However, our recent study shows that determination of the vacA genotypes for the combination of three regions (the s, m, and i regions) did not provide any advantage as a disease determinant marker over determination of s-and

Background. Thailand is at the cultural cross roads between East and South Asia. It has been suggested that this is also the region where the predominant Helicobacter pylori (H. pylori) genotype changes from East Asian to South Asian. Methods. We compared the molecular epidemiology and outcome of H. pylori infections among different ethnic groups in Thailand (Thai, Thai-Chinese and Chinese). H. pylori isolates were genotyped by polymerase chain reaction based on cagA, cag right end junction and vacA genotypes. Results. Ninety-eight isolates from 38 ethnic Thai, 20 ethnic Chinese and 40 Thai-Chinese were categorized into East Asian (45%), South/Central Asian (26%), Western (1%) or mixed type (29%). The East Asian genotype was the most common among Chinese (85%) and Thai-Chinese (55%) (p <.01 compared to ethnic Thai). The ethnicity of the mother among mixed Thai-Chinese marriages predicted the genotype of the child's H. pylori (e.g. when the mother was Chinese, 84% had East Asian type vs. 29% when the mother was Thai) (p <.001). Gastric cancer was common among ethnic Chinese with East Asian genotype (e.g. all Chinese with gastric cancer or peptic ulcer disease had East Asian genotype, whereas only 40% of Chinese with gastritis had this genotype). Conclusions. Immigration, intermarriage and the variety of H. pylori genotypes in Thailand suggest that Thailand is an ideal site for epidemiological studies attempting to relate H. pylori genotypes and host factors to outcome. Our data also support the hypothesis that the primary caretaker of the children is most likely the source of the infection.

BackgroundInfection with cagA-positive, cagA EPIYA motif ABD type, and vacA s1, m1, and i1 genotype strains of Helicobacter pylori is associated with an exacerbated inflammatory response and increased risk of gastroduodenal diseases. However, it is unclear whether the prevalence and virulence factor genotypes found in Southeast Asia are similar to those in Western countries. Here, we examined the cagA status and prevalence of cagA EPIYA motifs and vacA genotypes among H. pylori strains found in Southeast Asia and examined their association with gastroduodenal disease.MethodsTo determine the cagA status, cagA EPIYA motifs, and vacA genotypes of H. pylori, we conducted meta-analyses of 13 previous reports for 1,281 H. pylori strains detected from several Southeast Asian countries.ResultsThe respective frequencies of cagA-positive and vacA s1, m1, and i1 genotypes among examined subjects were 93% (1,056/1,133), 98% (1,010/1,033), 58% (581/1,009), and 96% (248/259), respectively. Stratification showed significant variation in the frequencies of cagA status and vacA genotypes among countries and the individual races residing within each respective country. The frequency of the vacA m-region genotype in patients infected with East Asian-type strains differed significantly between the northern and southern areas of Vietnam (p < 0.001). Infection with vacA m1 type or cagA-positive strains was associated with an increased risk of peptic ulcer disease (odds ratio: 1.46, 95%CI: 1.01-2.12, p = 0.046 and 2.83, 1.50-5.34, p = 0.001, respectively) in the examined Southeast Asian populations.ConclusionsBoth Western- and East Asian-type strains of H. pylori are found in Southeast Asia and are predominantly cagA-positive and vacA s1 type. In Southeast Asia, patients infected with vacA m1 type or cagA-positive strains have an increased risk of peptic ulcer disease. Thus, testing for this genotype and the presence of cagA may have clinical usefulness.