The M235T polymorphism of the AGT gene modifies the risk of coronary artery disease associated with the presence of hypercholesterolemia.
OBJECTIVE
Atherosclerosis is an inflammatory disease resulting from interactions between various genetic and non-genetic factors. Angiotensinogen gene (AGT) belongs to polymorphic candidate genes. Recent evidence show that many traditional risk factors of coronary artery disease (CAD) influence synthesis of AGT. This report focuses on the interactions between M235T polymorphism of AGT gene and traditional risk factors of CAD.


METHODS
255 subjects, including 158 patients with angiographically confirmed CAD and 97 blood donors without history of cardiovascular diseases were studied. M235T polymorphism of the AGT gene was genotyped using PCR-RFLP method. To determine the possible interactions of AGT genotypes and traditional risk factors of CAD the attributable proportion due to interaction (AP) and synergy models were used.


RESULTS
The frequency of 235T allele carriers was significantly higher in patients than in controls (77.8 vs. 62.9, OR = 2.20, 95% CI; 1.10-4.40, P = 0.026, in multivariate logistic regression model). We found the existence of interaction between the 235T allele carrier-state and hypercholesterolemia (total cholesterol > or = 5 mmol/l) increasing the risk of CAD (SI = 3.39, 95% CI; 1.33-8.66, AP = 0.65, 95% CI; 0.39-0.91). The 235T allele also interacted with elevated LDL cholesterol levels (> or = 3 mmol/l) (AP = 0.49, 95% CI; 0.20-0.96), but not with the hypertension, overweight/ obesity and cigarette smoking.


CONCLUSIONS
The 235T allele increases the risk of CAD associated with the presence of hypercholesterolemia.
Niemiec
Pawel
P
Department of Biochemistry and Medical Genetics, Medical University of Silesia, Medykow Str 18, 40-752 Katowice, Poland. pniemiec@slam.katowice.pl
Zak
Iwona
I
Wita
Krystian
K
D000328:Adult; D000808:Angiotensinogen / Q000235:genetics*; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011044:Poland / Q000453:epidemiology; D011110:Polymorphism, Genetic; D011859:Radiography; D012307:Risk Factors
D000808:Angiotensinogen