The CAT-262 C>T, MnSOD Ala16Val, GPX1 Pro198Leu Polymorphisms Related to Oxidative Stress and the Presence of Gastric Lesions

Abstract

Background & Aims: The increased oxidative stress plays an important role in gastro-duodenal ulcers and gastric cancer occurrence. We investigated the association between the genetic polymorphisms of genes encoding the antioxidative enzymes CAT, GPX and SOD and the occurrence of gastric lesions, considering also the environmental risk factors such as H. pylori infection, drug exposure, smoking and alcohol consumption.Methods: We included 373 patients who underwent endoscopy for symptoms, anemia or bleeding investigation. A complete set of demographical, clinical and pathological data was recorded. All patients were successfully genotyped.Results: In the multivariate logistic regression model, the patients having Pro/Pro genotype of GPX1 gene polymorphism had more severe gastric lesions as compared with patients with the Leu/Pro or Leu/Leu genotype (OR= 1.89, 95%CI: 0.99-3.57, p=0.051). The GPX1 Pro198Leu and the MnSOD Ala16Val gene polymorphism could be independent risk factors for reactive gastropathy changes, as shown by their association very close tostatistical significance (p=0.059 and p=0.054, respectively). Consumption of anticoagulants was a significant independent predictor (p=0.023, OR:0.43 95%CI:0.21-0.89) for the absence of active gastritis, while low-dose aspirin consumption was a risk factor for active gastritis in biopsy samples (p=0.025, OR:1.71, 95%CI:1.07-2.74).Conclusion: The variant genotype of GPX1Pro198Leu was associated with an increased risk for reactive gastropathy changes in gastric biopsies and with less severe endoscopic lesions, while MnSODAla16Val variant genotype (Val/Val or Val/Ala) seems to be related to the reactive gastropathy. However, none of them were associated with inflammatory or premalignant gastric lesions.

Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

“…SOD is involved in the inhibition of the HOCl and NO/peroxynitrite signaling pathways, enhancing the survival of the already transformed cells from apoptosis [124]. Negovan et al (2018) demonstrated that MnSOD Ala16Val polymorphism might be associated with a higher risk of reactive gastropathy [125]. H. pylori SOD inhibits the production of the proinflammatory cytokines (by downregulating the nuclear factor kappa B (NF-κB) activation pathways), as well as macrophage inflammatory protein 2 (MIP-2) (IL-8 homolog) via activation of the macrophages [126].…”

Helicobacter pylori and cytokine gene variants as predictors of premalignant gastric lesions

“…A study of gene polymorphisms involved in oxidative stress (of CAT , MnSOD and GPX1 genes) in relation to premalignant gastric lesions demonstrated contradictory results in different populations[122-124], despite the accepted role of oxidative stress as a consequence of H. pylori being a contributing factor in gastric carcinogenesis[118]. The gene variants of glutathione S-transferases (GSTs) involved in the metabolism of carcinogens, drugs, and reactive oxygen species were shown to be involved in GC predisposition, but with discordant results[125].…”

The Influence of GPX1 Pro198Leu, CAT C262T and MnSOD Ala16Val Gene Polymorphisms on Susceptibility for Non-Hodgkin Lymphoma and Overall Survival Rate at Five Years from Diagnosis

“…The DNA absorbance was verified by spectrophotometric quantification (BioSpectometer, Eppendorf, Germany). In order to analyze the genotypes of the mentioned SNPs, RFLP-PCR technique was performed using specific primers and FastDigest restriction enzymes, as previously reported [18,23,24].…”