Genetic variations of renin-angiotensin and fibrinolytic systems and susceptibility to coronary artery disease: a population genetics perspective.

BACKGROUND

Genetic predisposition is an important risk factor in coronary artery disease (CAD).This study was conducted to determine the polymorphism frequencies of the plasminogen activator inhibitor-1(PAI-1) gene 4G/5G, angiotensin-converting enzyme (ACE) gene I/D, and angiotensin II type 1 receptor (AT1) gene A1166C genotypes and to examine the role of these polymorphisms in CAD.

METHODS

Genomic DNAs obtained from 260 subjects (130 CAD patients and 130 control) were used in the study. ACE I/D and PAI-1 4G/5G polymorphism genotypes were determined using polymerase chain reaction (PCR) and electrophoresis. AT-1 A1166C polymorphism was determined using the PCR, restriction fragment length polymorphism (RFLP) and electrophoresis. The products amplified from AT1 gene by PCR were cut with HindIII restriction endonuclease and then analyzed by 2% agarose gel electrophoresis. The results were statistically analyzed with the chi-square test, Mann-Whitney U test, and independent two-sample t-test.

RESULTS

Allele frequencies showed statistically significant differences between the patient and control groups. There was no statistically significant difference in ACEI/D genotype frequencies between the twogroups. Likewise, no statistically significant difference was found in the AT1 A1166C genotype frequencies; however, a statistically significant difference was found in allele frequencies. The PAI-1 4G/5G genotype frequency was significantly higher in the patient group.

CONCLUSIONS

While there is a relationship between of PAI-1 gene 4G/5G polymorphism and CAD, ACE gene I/D and AT1 gene A1166C polymorphisms are not related. PAI-1 gene homozygous genotypes may be considered as a prognostic marker for CAD patients.