cagA-positive Helicobacter pylori and human NOS2-954G/C polymorphism: A possible association with severe clinical outcomes in Iranian patients

Helicobacter pylori infects more than 50% of the global population. The diversity and severity of clinical outcomes are attributed to the complex interaction among pathogen, host, and environmental factors. This study investigated the association between H. pylori virulence genes ( cagA , vacA , and dupA ) and human host NOS2 -954G/C polymorphism with clinical outcomes in H. pylori -infected Iranian patients. Polymerase chain reaction (PCR) was performed on 193 H. pylori culture-positive biopsy samples to determine the presence of cagA , vacA , and dupA genotypes. The NOS2 -954G/C polymorphism were assessed using PCR–restriction fragment length polymorphism (PCR-RFLP) on blood samples collected from 98 patients. The cagA and dupA genes were detected in 71.5% and 69.9% of isolates, respectively, and were more frequently found in strains derived from patients with peptic ulcer disease (PUD). The distribution of vacA polymorphisms was as follows: s1 / s2 (82.9% / 17.1%), m1 / m2 (44.6% / 55.4%), and i1 / i2 (52.3% / 47.7%). Analysis of NOS2 -954G/C polymorphism revealed the following genotypes: G/G (13.3%), G/C (81.6%), and C/C (5.1%). Notably, all 16 isolates obtained from gastric cancer (GC) patients exhibited the G/C genotype. Our findings suggest a borderline association between cagA -positive H. pylori isolates and disease severity, particularly PUD ( p = 0.045), whereas a stronger and statistically significant association was observed for the human NOS2 − 954G/C polymorphism ( p = 0.003). These results should be interpreted with caution, especially for outcomes with limited sample size. • The prevalence of the cagA and dupA genes was found to be high, at 71.5% and 69.9%, respectively, with these genes being more frequently observed in isolates derived from patients with peptic ulcer disease (PUD). • The distribution of vacA polymorphisms was as follows: s1/s2 (82.9% / 17.1%), m1/m2 (44.6% / 55.4%), and i1/i2 (52.3% / 47.7%). • The analysis of NOS2-954G/C polymorphism revealed the following genotype frequencies: G/G (13.3%), G/C (81.6%), and C/C (5.1%). • Our findings suggest a borderline association between cagA -positive Helicobacter pylori isolates and disease severity, particularly PUD ( p = 0.045), whereas a stronger and statistically significant association was observed for the human NOS2 − 954G/C polymorphism ( p = 0.003).