Helicobacter Pylori Diversity in Gastric Cancer and GERD Among Singapore Chinese Population

Abstract

Introduction: H.pylori (Hp) infection leads to divergent clinical outcomes like PUD, chronic gastritis, gastric cancers (GC) and GERD. Bacterial factors, host factors, combination of both and environmental factors play major role in establishing the disease. We hypothesize that diverse genetic factors cause GC and GERD in our population. Aim: To determine various genotypes associated with GC and GERD among Singaporean Chinese population. Materials & Methods: H.pylori was cultured from 182 Chinese patients (52GC, 70 gastritis & 60 GERD) were analyzed in this prospective, on-going study. DNA was extracted, sequence analysis and genotyping was performed using specific gene primers of various virulence factors such as cagPAI, vacAs1, s2, m1, m2, cagE, babA2, sabA and oipA. Results: Univariate and multivariate analysis revealed that cagPAI, cagE, babA2, sabA and oipA were significant among GC when compared with gastritis (p < 0.001). oipA “on” status was significantly associated with expression of cagPAI and suppression of sabA (p < 0.01). Sequence analysis of representative Hp strains indicated that cagPAI, cagE, babA2, sabA and oipA oipA exhibited >92% identity to previously published data. Univariate analysis of GERD revealed that cagE, babA2 and oipA were significant (P < 0.01), whereas, multivariate analysis revealed that none of the genotypes were significant. Conclusion: Our on-going, prospective study indicates that Hp genetic diversity is related to clinical presentation. Virulence factors associated with GC were: CagPAI, CagE and outer membrane proteins (SabA, OipA, babA2). Host factors may have a moderating role in the clinical manifestation of Hp infection. Majority of oipA genotype is detected at functional status. The “on” status was significantly related to gastric cancer. This could probably be associated with enhanced interleukin-8 secretion and inflammation, important at initial stages of disease process. Further studies will be focused on measurement of levels of interleukin, OipA proteins or anti-OipA antibody in patients' sera, pathological assessment & oipA functional status and disease presentation. Hp strains from GERD patients did not significantly express any of the genotypes when compared to NUD patients. Our study suggests these genotypes may protect against the development of GERD in our population.