Renin-angiotensin system associated with risk of upper GI mucosal injury induced by low dose aspirin: renin angiotensin system genes' polymorphism.
BACKGROUND
We have previously shown that co-treatment of angiotensin type 1 receptor (AT1R) blocker (ARB) or angiotensin converting enzyme (ACE) inhibitor seem to reduce peptic ulcer among patients taking low dose aspirin. It is reported that a series of renin-angiotensin system (RAS) gene polymorphisms significantly influence the rate of the gene transcription.


OBJECTIVE
The aim of this study was to examine the genotypes of RAS genes related to the risk of peptic ulcer and ulcer bleeding among patients taking low dose aspirin.


METHODS
Patients taking 100 mg of aspirin who were planning to undergo endoscopy for surveillance or who had history of recent upper GI ulcer bleeding were included. ACE (Ins/Del), angiotensinogen (AGT; G-217A, A-20C, A-6G, T174 M, M235T), and AT1R (T-713G, C-521T, A1166C) genotypes were determined by PCR or PCR-RFLP.


RESULTS
Four hundred twenty-five patients were enrolled including 68 patients with peptic ulcer and 20 patients with ulcer bleeding. Co-treatment of ARB was significantly associated with peptic ulcer and ulcer bleeding. AGT-20 CC (adjusted OR 4.94, 95% CI 1.21-20.2) was significantly associated with ulcer bleeding. The CC genotype of AT1R-521 was significantly associated with peptic ulcer only in the subgroup taking neither ACE inhibitor nor ARB.


CONCLUSIONS
Co-treatment of ARB reduces peptic ulcer and bleeding among patients taking low dose aspirin. RAS may play an important role in the development of upper GI mucosal injury induced by low dose aspirin.
Shiotani
Akiko
A
Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan. shiotani@med.kawasaki-m.ac.jp
Nishi
Ryuji
R
Yamanaka
Yoshiyuki
Y
Murao
Takahisa
T
Matsumoto
Hiroshi
H
Tarumi
Ken-ichi
K
Kamada
Tomoari
T
Sakakibara
Takashi
T
Haruma
Ken
K
D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000235:genetics; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D005838:Genotype; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010437:Peptic Ulcer / Q000139:chemically induced / Q000235:genetics; D010438:Peptic Ulcer Hemorrhage / Q000139:chemically induced / Q000235:genetics; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000235:genetics* / Q000502:physiology
D000897:Anti-Ulcer Agents; D005343:Fibrinolytic Agents; D001241:Aspirin
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