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血管紧张素转换酶(ACE)基因在人左心室中的表达:ACE基因插入/缺失多态性及左心室功能的影响

Angiotensin converting enzyme (ACE) gene expression in the human left ventricle: effect of ACE gene insertion/deletion polymorphism and left ventricular function.

作者信息

Davis G K, Millner R W, Roberts D H

机构信息

Regional Cardiothoracic Centre, Victoria Hospital, Blackpool, UK.

出版信息

Eur J Heart Fail. 2000 Sep;2(3):253-6. doi: 10.1016/s1388-9842(00)00070-2.

DOI:10.1016/s1388-9842(00)00070-2
PMID:10938484
Abstract

AIMS

We investigated the effect of the angiotensin converting enzyme (ACE) I/D polymorphism and left ventricular (LV) function on ACE gene expression in tru-cut LV myocardial biopsies from 50 consecutive patients (II: 18, ID: 18, DD: 14; 40 males) with ischaemic heart disease undergoing coronary artery bypass grafting (CABG).

METHODS

The polymerase chain reaction was used for ACE genotyping. LV function [normal (n=22) or impaired] was determined by left ventriculography at cardiac catheterisation prior to bypass surgery. ACE expression was determined (n=46) by a competitive quantitative reverse transcription PCR assay using 5x10(5), 12. 5x10(5) and 20x10(5) copies of a mutant DNA internal standard (IS). PCR products were analysed by negative film photography and laser densitometry to determine the number of ACE transcripts present.

RESULTS

Mean age was similar (II: 59.1+/-10.4, ID: 57.0+/-10.6, DD: 61.4+/-6.2; P=NS) with no differences between groups in sex (P=0. 25); hypertension, P=0.31; previous myocardial infarction, P=0.44; LV function, P=0.23; and ACE inhibitor therapy, P=0.06. ACE expression per 100 ng of total RNA varied with genotype [<5x10(5) copies in II: 6, 5-12.5x10(5) copies in II: 6, ID: 16, DD: 4; and >12.5x10(5) (II: 4, ID: 2, DD: 8), Kendall's tau-b coefficient (tau(b))=0.43, P=0.003]. Impaired LV function also correlated with higher levels of ACE expression, Kendall's tau(b)=0.40, P=0.001.

CONCLUSION

ACE gene expression in the left ventricle varied with ACE genotype and LV function in IHD patients undergoing CABG.

摘要

目的

我们研究了血管紧张素转换酶(ACE)I/D多态性和左心室(LV)功能对50例连续接受冠状动脉搭桥术(CABG)的缺血性心脏病患者经皮穿刺LV心肌活检中ACE基因表达的影响。这些患者中,II型18例、ID型18例、DD型14例;男性40例。

方法

采用聚合酶链反应进行ACE基因分型。在搭桥手术前通过心导管检查时的左心室造影确定LV功能[正常(n = 22)或受损]。使用5×10⁵、12.5×10⁵和20×10⁵拷贝的突变型DNA内标(IS),通过竞争性定量逆转录PCR测定法确定ACE表达(n = 46)。通过负片摄影和激光密度测定法分析PCR产物,以确定存在的ACE转录本数量。

结果

平均年龄相似(II型:59.1±10.4,ID型:57.0±10.6,DD型:61.4±6.2;P =无显著性差异),各组间性别(P = 0.25)、高血压(P = 0.31)、既往心肌梗死(P = 0.44)、LV功能(P = 0.23)和ACE抑制剂治疗(P = 0.06)均无差异。每100 ng总RNA中的ACE表达随基因型而变化[II型中<5×10⁵拷贝的有6例,II型中5 - 12.5×10⁵拷贝的有6例,ID型16例,DD型4例;>12.5×10⁵拷贝的(II型4例,ID型2例,DD型8例),肯德尔tau - b系数(tau(b))= 0.43,P = 0.003]。LV功能受损也与较高水平的ACE表达相关,肯德尔tau(b)= 0.40,P = 0.001。

结论

接受CABG的缺血性心脏病患者左心室中的ACE基因表达随ACE基因型和LV功能而变化。

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