VKORC1-1639 G>A Polymorphism and the Risk of Non-Variceal Upper Gastrointestinal Bleeding.
OBJECTIVE
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).


CONCLUSIONS
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.
3rd Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Ioana
I
Groza
3rd Medical Clinic; Prof. Dr. Octavian Fodor Regional Institute of Gastroenterology-Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Dana
D
Matei
3rd Medical Clinic; Prof. Dr. Octavian Fodor Regional Institute of Gastroenterology-Hepatology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Marcel
M
Tantau
Department of Genetics, Iuliu Hatieganu University of Medicine and Pharmacy;Department of Genetics, Ion Chiricuta Oncology Institute, Cluj Napoca, Romania.
Adrian P
AP
Trifa
5th Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Sorin
S
Crisan
Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania. stefanvesa@gmail.com.
Stefan C
SC
Vesa
Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Corina
C
Bocsan
Department of Pharmacology, Toxicology and Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Anca D
AD
Buzoianu
3rd Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Monica
M
Acalovschi
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001241:Aspirin / Q000009:adverse effects; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D001241:Aspirin