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肾素-血管紧张素系统与小剂量阿司匹林诱导的上消化道黏膜损伤风险相关:肾素血管紧张素系统基因多态性。

Renin-angiotensin system associated with risk of upper GI mucosal injury induced by low dose aspirin: renin angiotensin system genes' polymorphism.

机构信息

Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan.

出版信息

Dig Dis Sci. 2011 Feb;56(2):465-71. doi: 10.1007/s10620-010-1382-3. Epub 2010 Sep 8.

Abstract

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.

AIM

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.

摘要

背景

我们之前的研究表明,血管紧张素 1 型受体(AT1R)阻滞剂(ARB)或血管紧张素转换酶(ACE)抑制剂的联合治疗似乎可以降低低剂量阿司匹林治疗患者的消化性溃疡发生率。据报道,一系列肾素-血管紧张素系统(RAS)基因多态性显著影响基因转录率。

目的

本研究旨在检测与低剂量阿司匹林治疗患者发生消化性溃疡和溃疡出血风险相关的 RAS 基因的基因型。

方法

纳入计划接受内镜监测或近期有上消化道溃疡出血史的服用 100mg 阿司匹林的患者。采用 PCR 或 PCR-RFLP 法检测 ACE(Ins/Del)、血管紧张素原(AGT;G-217A、A-20C、A-6G、T174M、M235T)和 AT1R(T-713G、C-521T、A1166C)的基因型。

结果

共纳入 425 例患者,其中 68 例患有消化性溃疡,20 例患有溃疡出血。ARB 的联合治疗与消化性溃疡和溃疡出血显著相关。AGT-20CC(调整后的 OR 4.94,95%CI 1.21-20.2)与溃疡出血显著相关。仅在未服用 ACE 抑制剂和 ARB 的亚组中,AT1R-521CC 基因型与消化性溃疡显著相关。

结论

ARB 的联合治疗可降低低剂量阿司匹林治疗患者的消化性溃疡和出血发生率。RAS 可能在上消化道黏膜损伤的发生中起重要作用低剂量阿司匹林诱导。

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