Aspirin-induced peptic ulcer and genetic polymorphisms.
There are a few studies of the association between genetic polymorphisms and the risks of acetylsalicylic acid (aspirin)-induced ulcer or its complications. Two single nucleotide polymorphisms (SNP) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibited increased sensitivity to aspirin and had lower prostaglandin synthesis capacity, lacking statistical significance in the association with bleeding peptic ulcer. A recent Japanese study indicated that the number of COX-1-1676T alleles was a significant risk factor for peptic ulcer in users of non-steroidal anti-inflammatory drugs (NSAIDs). There are some genetic polymorphisms for aspirin resistance, such as platelet membrane glycoproteins, thromboxane A2 (TXA2) receptor, platelet activating factor acetylhydrolase and coagulation factor XIII; however, data on the frequency of gastrointestinal (GI) events in these variants are lacking. Carrying the CYP2C9 variants is reported a significantly increased risk of non-aspirin NSAID-related GI bleeding. The polymorphisms of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) have been associated with development of peptic ulcer or gastric cancer. In a recent investigation, carriage of the IL-1beta-511 T allele was significantly associated with peptic ulcer among low-dose aspirin users. Hypoacidity in corpus gastritis related to polymorphisms of pro-inflammatory cytokines seems to reduce NSAIDs or aspirin-related injury. Data on which polymorphisms are significant risk factors for GI events in aspirin users are still lacking and further large-scale clinical studies are required.
Shiotani
Akiko
A
Department of Internal Medicine, Kawasaki Medical School, Matsushima Kurashiki City, Okayama, Japan. shiotani@med.kawasaki-m.ac.jp
Sakakibara
Takashi
T
Nomura
Maki
M
Yamanaka
Yoshiyuki
Y
Nishi
Ryuji
R
Imamura
Hiroshi
H
Tarumi
Ken-ichi
K
Kamada
Tomoari
T
Hata
Jiro
J
Haruma
Ken
K
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001241:Aspirin / Q000009:adverse effects*; D051545:Cyclooxygenase 1 / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D016207:Cytokines / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D010437:Peptic Ulcer / Q000139:chemically induced* / Q000235:genetics*; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D018836:Inflammation Mediators; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase; D001241:Aspirin