VKORC1-1639 G>A Polymorphism and the Risk of Non-Variceal Upper Gastrointestinal Bleeding
download Full Article (PDF file) Ioana Groza1, Dana Matei1,2, Marcel Tanţău1,2, Adrian P. Trifa3,4, Sorin Crişan5, Ştefan C. Vesa6, Corina Bocşan6, Anca D. Buzoianu6, Monica Acalovschi1
1) 3rd Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy;
2) Prof. Dr. Octavian Fodor Regional Institute of Gastroenterology-Hepatology;
3) Department of Genetics, Iuliu Hatieganu University of Medicine and Pharmacy;
4) Department of Genetics, Ion Chiricuta Oncology Institute, Cluj Napoca;
5) 5th Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy;
6) Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
ABSTRACT Background & Aims: The mutations in the gene that encodes vitamin K epoxide reductase (VKOR) enzyme are responsible for low levels of vitamin K. The purpose of this study was to evaluate whether the presence of the VKORC1 -1639 G> A polymorphism is a risk factor for non-variceal upper gastrointestinal bleeding (UGIB) in patients without concomitant therapy with vitamin K antagonists. Methods: This case-control study comprised 163 consecutive patients diagnosed with UGIB and 178 controls, in whom the diagnosis of UGIB was excluded. The following data were recorded: age, gender, alcohol consumption, smoking, history of UGIB, nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin consumption. Genetic analysis included genotyping for the VKORC1 -1639 G>A polymorphism. Results: History of UGIB (OR 3.463, CI95% 1.463-8.198, p=0.005), smoking (OR 2.498, CI95% 1.358-4.597, p=0.003), alcohol consumption (OR 3.283, CI95% 1.796-6.000, p<0.001), use of NSAIDs (OR 4.542, CI95% 2.502-8.247, p<0.001) or of low-dose aspirin (OR 2.390, CI95% 1.326-4.310), and the VKORC1 -1639 G> A AA genotype (OR 1.364, CI95% 0.998-1.863, p=0.05) were associated with an increased risk of UGIB. The risk of UGIB was analyzed in patients with genotype AA who used aspirin or NSAIDs. The genotype AA has not kept its status of independent risk factor (p=0.3). In subjects with NSAIDs/aspirin therapy and genotype AA there was a two times higher chance of UGIB compared to those under NSAIDs/aspirin therapy alone (OR 7.6 vs. 3.6, p<0.001). Conclusion: Patients with non-variceal UGIB caused by the use of NSAIDs or low-dose aspirin are more frequent carriers of the VKORC1 -1639 G>A AA genotype, as compared to those without UGIB.
Key words: non-variceal upper gastrointestinal bleeding – VKORC1 – 1639 G>A polymorphism – NSAIDs – risk factors. Abbreviations: NSAIDs: nonsteroidal anti-inflammatory drugs; OR: odds ratio; PIVKA: proteins induced by vitamin K absence; PPIs: proton pump inhibitors; UGIB: upper gastrointestinal bleeding; VKORC1: vitamin K epoxide reductase subunit C1.