AGT A-20C (rs5050) gene polymorphism and ulcer occurrence in patients treated with low-dose aspirin: a case-control study / Polimorfismul AGT A-20C și ulcerele gastro-duodenale la pacienții sub tratament cu aspirină în doze antiagregante: studiu caz-control

Genetic factors may play a role in prediction of gastrointestinal side effects of aspirin, one of the most used drugs worldwide. We aim to determine a possible correlation between AGT A-20C (rs5050) gene polymorphism and gastro-duodenal ulcer in patients taking low-dose aspirin, adjusted for clinical and histological characteristics.

Results. We enrolled 211 patients stratified according to AGT A-20C genotype: 122 AA, 83 AC and 6 CC patients. There were no significant differences regarding demographical and clinical parameters, except for the frequency of ulcers (4%, 8.4% respective 50%, p=0.03), endoscopic bleeding signs (12.3%, 14.5% respective 50%, p=0.0001) and the frequency of gastritis in biopsy (63.9%, 54.2% respective 16.7%, p=0.03) in genotype groups. When we compared ulcer and non-ulcer group, variant homozygous CC genotype carried an increased risk for ulcer (OR:9.66, 95% CI: 1.46-63.7, p=0.04) than AA group, as well as variant C allele compared with normal A allele (OR: 2.12, 95% CI: 1.07-4.63, p=0.04). On multivariate analysis, variant homozygous CC genotype AGT A-20C showed an OR: 12.32 (95% CI:1.40 -108.13, p=0.02) for ulcer, while H. pylori infection (OR:2.40, 95% CI:1.18 -6.54, p=0.04) and concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (OR:1.31, 95% CI:1.07 - 2.27, p=0.05) remained predictors for ulcer in aspirin consumers.

Conclusions. Variant C allele and variant homozygous CC genotype AGT A-20C, infection with H. pylori and NSAIDs co-treatment are risk factors for gastro-duodenal ulcer in low-dose aspirin consumers. The variant homozygous CC genotype AGT A-20C patients treated with LDA are more prone to have reactive gastropathy and bleeding ulcers in a population with a high prevalence of H. pylori infection