H. pylori is one of the most successful pathogens that colonizes the stomach of half the world's population. This bacterium can cause serious clinical consequences such as chronic gastritis, PU disease, gastric atrophy and GC (32). According to documents, approximately 63% of GC cases worldwide are caused by H. pylori infection, and the bacterium is also responsible for 75% of gastric ulcers and 90% of duodenal ulcers (25). The strains of this bacterium are genetically diverse and harbor different virulence genes (33, 34). Studies in recent decades have shown that these genes are strain-specific (e.g. vacA, cagA, and omp) and play an important role in the immunopathogenesis of H. pylori and in the development of serious clinical outcomes (12, 16, 20, 25, 30, 35). In several studies, the role of the homB gene in the pathogenesis of this pathogen was controversial; difference in results are related to differences in diet, environmental condition, hygiene status, age, socioeconomic level, and low sample size (27, 36). Nevertheless, in the present study, we conducted a comprehensive literature review to assess the role of homB in the progression of primary infection to PU and CG diseases in Western and Asian countries. Oleastro et al. in their study showed that the presence of the homB gene is significantly higher than the homA gene in Portuguese children with PU disease; “on” genotypes consistent cagA/vacAs1/ hopQI/oipA/homB strongly were associated with PU disease in children under four years of age (20). In contrast, in studies on populations of Iraq, Turkey, and South Korea, none of homA and homB genes were correlated with PU disease (24, 37). Interestingly, all studies in Western children have shown that the homB gene is associated with PU disease, while the homA gene is more prevalent in the NUD (19, 20, 23). In present study, frequency of homB gene in patients with affected to PU and GC, severe clinical outcomes significantly was more prevalent than gastritis/NUD cases (54.4% and 39.7%, respectively). In addition, the summary OR showed that there was a significant relationship between homB-positive genotype and progression to PU disease, especially in Western countries (OR: 1.16; 1.20–2.14 with 95% CIs; p value: 0.01), while in Asian countries there was no such relationship (OR: 0.89; 0.57–1.40 with 95% CIs; p value: 0.01). Therefore, our findings confirmed the results of previous studies. Also, strains isolated from Western countries contained two copies of the homB gene, but most infectious strains in Asian countries had only one copy of each of the homA and homB genes (18, 20, 29). Related articles showed that the number of OMP copies also affects the status of bacterial compatibility and plays a role in the formation of clinical outcomes (13, 38, 39). Recently, the role of homB as a cofactor in the increase of gastric adenocarcinoma in Asian countries has attracted much attention. The homB gene enhances the attachment of H. pylori to gastric epithelium, leading to dysregulation of normal signaling pathways and genetic instability (25, 37). In addition, this gene increases the risk of GC through interferences such as inducing the inflammatory response, persistent infection, and gastric atrophy (21). Abadi et al. showed that 78% of the strains isolated from GC patients contained the homB gene (25). Jung et al. found that cagA-independent homB was associated with GC in Western countries (21). However, in a study on the Chinese population, despite the presence of the homB gene in all isolated strains in patients with PU disease and GC, no significant correlation was observed (36). According to our results, a strong correlation was observed between the homB gene and the risk of GC in the Asian population (OR: 3.71; 1.85–7.45 with 95% CIs; p value: 0.01), whereas this correlation did not exist in Western countries (OR: 1.42; 0.79–2.54 with 95% CIs; p value: 0.66). Thus, depending on the geographical area, the homB gene appears to lead to PU and GC in Western and Asian countries respectively. In several studies, correlation between homB and other virulence factors, especially vacA, cagA, oipA, hopQI, and babA in patients with PU and GC was investigated. Sterbenc et al. in their study observed that there was no significant difference in the histopathological characteristics of PU disease in both groups of children with and without the genotype profiles vacAs1m1/cagA/babA2/hompB (27). Similar to this study, Oleastro et al. found that homB, independent of the cagA+/vacAs1 genotype profile, increases PU disease risk in Western countries (22). However, in other studies, it was shown that there is a significant correlation between homB and cagA, and homB also acts as a cofactor in complications such as PU and PUD (21, 25, 37). Due to the lack of raw data and uncertain results, we could not evaluate the relationship between homB and cagA in patients with PU, but in GC cases, a weak correlation was observed (OR: 1.47; 0.95–2.28 with 95% CIs; p value: 0.79; I2: 80.15; Q-Value: 15.1; p value: 0.02; Egger’s p value: 0.07; Begg’s p value: 0.08). In the end it must be said, our study had several limitations such as low sample size, low number of included studies, inaccessibility to raw data, high heterogeneity in some studies, and also slight publication bias based on asymmetry of funnel plot. Hence, we need further studies to confirm the present findings.