Angiotensin-converting enzyme (ACE) gene polymorphisms in patients characterised by coronary angiography.
The angiotensin converting enzyme (ACE) gene is implicated as a risk factor for coronary artery disease and myocardial infarction (MI). An insertion/deletion (I/D) polymorphism is believed to be in linkage disequilibrium with a functional site elsewhere. Ten polymorphisms have recently been identified in the ACE gene. We screened patients undergoing coronary angiography (n = 258) for six of these polymorphisms (T-5491C, T-93C, A-240T, T1237C, D/I and 4656(CT)2/3), and identified a further two rare polymorphisms. ACE levels were associated with genotype for all polymorphisms analysed individually by one way ANOVA (P < 0.0005). The polymorphisms occurring in the 5' region were in negative linkage disequilibrium with the exonic and 3' region polymorphisms. The A-240T polymorphism had the greatest association with ACE levels (R2 = 14%); none of the others were significantly associated with levels when adjustment was made for A-240T. None of the polymorphisms were associated with the extent of coronary atheroma. Two of the promoter polymorphisms (A-240T and T-93C) were weakly related to the occurrence of MI (P = 0.03 and P = 0.05, respectively, by chi 2 analysis). The TT genotype of A-240T appeared to be protective against MI with an odds ratio of 0.31 (95% confidence interval, 0.12, 0.83). These findings indicate that polymorphisms in the ACE gene promoter region may have a stronger association with disease than the I/D polymorphism.
Foy
C A
CA
Unit of Molecular Vascular Medicine, University of Leeds, Leeds General Infirmary, UK.
Rice
G I
GI
Ossei-Gerning
N
N
Mansfield
M W
MW
Grant
P J
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002637:Chest Pain; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational
D007703:Peptidyl-Dipeptidase A