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


CONCLUSIONS
ACE gene expression in the left ventricle varied with ACE genotype and LV function in IHD patients undergoing CABG.
Regional Cardiothoracic Centre, Victoria Hospital, Blackpool, UK. gershan@hotmail.com
G K
GK
Davis
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Millner
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Roberts
D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D005819:Genetic Markers; D005838:Genotype; D006352:Heart Ventricles / Q000201:enzymology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D017202:Myocardial Ischemia / Q000201:enzymology / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016277:Ventricular Function, Left / Q000235:genetics*
D005819:Genetic Markers; D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A