Effect of a specific cyclooxygenase-gene polymorphism (A-842G/C50T) on the occurrence of peptic ulcer hemorrhage.
Cyclooxygenases (COX) catalyze the conversion of arachidonic acid to prostaglandins (PGs). COX-inhibiting drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), increase the risk for peptic ulcer disease. As a corollary, COX gene polymorphisms could be important in the pathogenesis of peptic ulcer disease because these affect prostaglandin formation and impair its protective effect at the level of the gastric mucosa. This study was designed to investigate the association between the functional single-nucleotide polymorphism, A-842G/C50T, in the COX-1 gene and peptic ulcer bleeding. We obtained DNA samples from 106 patients who underwent upper gastrointestinal endoscopy because of bleeding peptic ulcer disease and from 88 healthy control subjects. Genetic polymorphism in A-842G/C50T was determined by PCR followed by restriction-fragment-length-polymorphism analysis. Adjusted logistic regression analysis was performed to evaluate the associations. Risk factors associated with peptic ulcer bleeding were male gender (odds ratio, 4.78; 95% confidence interval, 2.6-8.8) and NSAID/aspirin-use (odds ratio, 38.39; 95% confidence interval, 14.2-103.6). The A-842G/C50T heterozygote was less frequent in peptic ulcer bleeding (n = 7) compared with healthy control subjects (n = 11). The adjusted risk for peptic ulcer bleeding among individuals who were heterozygote for the A-842G/C50T polymorphism was 0.75 (range, 0.19-3.01) compared with wild type. The COX-1 A-842G/C50T SNP does not influence the risk for developing peptic ulcer bleeding.
van Oijen
Martijn G H
MG
Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands. M.vanOijen@mdl.umcn.nl
Laheij
Robert J F
RJ
Koetsier
Marjolein
M
de Kleine
Evelien
E
Te Morsche
René H M
RH
van Kerkhoven
Lieke A S
LA
Jansen
Jan B M J
JB
Drenth
Joost P H
JP
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D016022:Case-Control Studies; D051545:Cyclooxygenase 1 / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010438:Peptic Ulcer Hemorrhage / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D051545:Cyclooxygenase 1