Background: Gastritis is an inflammation of the stomach lining often caused by Helicobacter pylori infection. Among three H. pylori genes coding for hemolytic toxins, the clinical outcome of hp0499 and hp1490 is unclear. We conducted molecular and histological analyses to evaluate the correlation between these genes and gastritis severity. Methods: We analyzed the hp0499 and hp1490 variants of 116 Indonesian samples using next generation sequencing and validated them using polymerase chain reaction (PCR). The updated Sydney system was used to grade gastritis through histological analyses. We then calculated the influence of hp0499 and hp1490 on the gastritis severity, using multivariate analysis and cagA and vacA as major H. pylori virulence factors. Results: Two variants of each gene were identified and named hp0499-1 and -2, and hp1490-1 and -2. We noted that hp0499 expression was significantly correlated with corporal atrophy (p = 0.037). H. pylori hp1490 significantly correlated with antral acute and chronic inflammation as well as corporal density (p = 0.025, p = 0.07, p = 0.010, respectively). After adjusting for age and sex, we found that vacA s1m1 was an independent risk factor for acute antral inflammation (p = 0.032). hp1490 and vacA s1m1 were independent risk factors for chronic antral inflammation (p = 0.030 and p = 0.031, respectively). Conclusions: We identified the variants hp0499-1 and -2 and hp1490-1 and -2 and demonstrated that hp0499 plays a significant role in the severity of corporal atrophy. Moreover, hp1490 was characterized as an independent risk factor for chronic inflammation in the antral region. Therefore, hp0499 and hp1490 are new potential targets for therapeutics.
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