Angiotensin converting enzyme gene polymorphism is associated with severity of coronary artery disease in men with high total cholesterol levels.
This study examines whether renin-angiotensin-aldosterone system gene polymorphisms: ACE (encoding for angiotensin converting enzyme) c.2306-117_404 I/D, AGTR1 (encoding for angiotensin II type-1 receptor) c.1080*86A>C and CYP11B2 (encoding for aldosterone synthase) c.-344C>T are associated with the extension of coronary atherosclerosis in a group of 647 patients who underwent elective coronary angiography. The extension of CAD was evaluated using the Gensini score. The polymorphisms were determined by PCR and RFLP assays. The associations between genotypes and the extent of coronary atherosclerosis were tested by the Kruskal-Wallis test, followed by pairwise comparisons using Wilcoxon test. The population has been divided into groups defined by: sex, smoking habit, past myocardial infarction, BMI (>, ≤ 25), age (>, ≤ 55), diabetes mellitus, level of total cholesterol (>, ≤ 200 mg/dl), LDL cholesterol (>, ≤ 130 mg/dl), HDL cholesterol (>, ≤ 40 mg/dl), triglycerides (>, ≤ 150 mg/dl). Significant associations between the ACE c.2306-117_404 I/D polymorphism and the Gensini score in men with high total cholesterol levels (P(Kruskal-Wallis) = 0.008; P(adjusted) = 0.009), high level of LDL cholesterol (P(Kruskal-Wallis) = 0.016; P(adjusted) = 0.028) and low level of HDL cholesterol (P(Kruskal-Wallis) = 0.04; P(adjusted) = 0.055) have been found. No association between the AGTR1 c.1080*86A>C and CYP11B2 c.-344C>T and the Gensini score has been found. These results suggest that men who carry ACE c.2306-117_404 DD genotype and have high total cholesterol, high LDL cholesterol and low HDL cholesterol levels may be predisposed to the development of more severe CAD.
Department of Biology and Genetics, Medical University of Gdansk, Debinki 1, 80-211 Gdansk, Poland.
Joanna
J
Borzyszkowska
Anna
A
Stanislawska-Sachadyn
Marcin
M
Wirtwein
Wojciech
W
Sobiczewski
Dariusz
D
Ciecwierz
Radoslaw
R
Targonski
Marcin
M
Gruchala
Andrzej
A
Rynkiewicz
Janusz
J
Limon
D000328:Adult; D000368:Aged; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D019405:Cytochrome P-450 CYP11B2 / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000097:blood / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D018709:Statistics, Nonparametric
C544065:AGTR1 protein, human; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D044140:Receptor, Angiotensin, Type 1; D002784:Cholesterol; D019405:Cytochrome P-450 CYP11B2; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A