Cytotoxic-associated gene L (CagL) protein is a structural component of the type IV secretion system in Helicobacter pylori that plays a pivotal role in the translocation and secretion of CagA protein. However, the effect of this factor in severe gastroduodenal outcomes has not yet been demonstrated.

In the current study, using databases such as ISI Web of Science, PubMed and Scopus, we systematically investigated the role of cagL gene and its polymorphisms in the pathogenesis of H. pylori. Then, the logical relationship between cagL polymorphisms and frequency of gastrointestinal disorders such as gastric cancer and peptic ulcer disease (PUD) was measured.

In total, data from 1071 bacterial strains were evaluated. The prevalence of H. pylori cagL gene in patients with various forms of infections such as nonulcer dyspepsia, PUD, and gastric cancer was measured 81.9% [95% confidence interval (CI): 68.0–90.5], 94.0% (95% CI: 81.4–98.3), and 86.2% (95% CI: 73.8–93.3), respectively. We show that infection with bacteria harboring cagL gene increases the risk of PUD and gastric cancer by 3.7- and 1.7-fold, respectively. Moreover, CagL/CagA/(<2) EPIYA C repeats could increase the risk of severe gastrointestinal disorders by 7.1-fold. Among the all sequence variations of this gene, it was found that only mutations associated with amino acids at positions 122K/N (odds ratio: 0.1) and 134I/V (odds ratio: 0.23) significantly reduced the risk of PUD.

Our findings suggest that the presence of the cagL gene could potentially lead to severe gastrointestinal outcomes, particularly PUD and gastric cancer. However, although most polymorphisms of cagL have no a significant relationship with H. pylori-related diseases, but variants 122K/N and 134I/V play a protective role against PUD.