Helicobacter pylori (H. pylori) is the pivotal cause of chronic gastritis, peptic ulcer diseases (PUD) and gastric cancer. Morphologically, the bacterium is spiral, Gram-negative and microaerophilic which survives lifespan in the human stomach in case of weak antibiotic therapy. There is a major difference in the pattern of global prevalence of H. pylori infection based on different levels of urbanization, hygiene, sanitation, access to clean water and other socioeconomic factors. To date, many studies have attempted to find significant associations between specific gastroduodenal diseases and dupA-positive strains, but no conclusive conclusion has been declared. The main reason for these inconsistent findings is the various methodologies applied in experiments which in turn have resulted in inaccurate observation. Our analysis showed that the existence of various alleles located in the dupA cluster would be a novel explanation for different associations found between this bacterial gene and diseases. In detailed experiments examining our proposed alleles using a large number of patients can be useful to disclose a significant clinical association between H. pylori dupA-positive strains and duodenal ulcer.