Global epidemiology of <i>Helicobacter pylori iceA</i> genotypes: heterogeneity and virulence implications

ABSTRACT The contact-induced epithelium gene A ( iceA ), with allelic variants iceA1 and iceA2 , remains a controversial virulence factor in Helicobacter pylori due to inconsistent clinical outcomes. In this study, we analyzed 1,427 H. pylori genomes from the NCBI database and 200 clinical isolates from Shenzhen, China, to elucidate the global distribution of iceA genotypes and their associations with other virulence factors, bacterial gene expression, and the relationship with gastric diseases. We found that iceA genotypes varied significantly across regions, with iceA1 predominating in Asia and Europe, and iceA2 being more prevalent in North America. This suggests adaptive evolution to regional host environments. The association between iceA genotypes and cagA status also exhibited regional patterns. Additionally, iceA1 was linked to higher ureA expression, potentially enhancing acid resistance and colonization potential ( P &lt; 0.05). Importantly, patients infected with iceA1 genotype strains were more likely to present with gastric erosion ( P &lt; 0.05); however, they showed no association with peptic ulcer disease in any region. These findings highlight the geographical heterogeneity of iceA1 genotypes and their potential role in H. pylori -related gastric diseases. IMPORTANCE Our study found that the iceA1 genotype of Helicobacter pylori , which is relatively common in Asia, is associated with increased urea hydrolysis capacity and shows a specific association with erosive gastritis in Chinese patients. These findings suggest that iceA1 may potentially serve as an early biomarker for the identification of patients at risk of progressive gastric damage. Clinically, detecting iceA1 could improve risk stratification in high-prevalence regions, guiding more targeted monitoring and early intervention strategies. This research supports incorporating bacterial genotyping into clinical practice to optimize personalized treatment and prevent disease progression in susceptible populations.