Analysis Of The Renal Angiotensin System Gene Polymorphism In Patients With Coronary Heart Disease

To determine the relationship of 3 key component gene polymorphism of the RAS(Renin angiotensin system) to CHD (coronary heart disease) and the severity of coronary artery stenosis, we examined the I/D(insertion/deletion) polymorphism of the ACE(angiotensin converting enzyme) gene and the A1166/C polymorphism of the ATiR(angiotensin II type 1 receptor) gene and the M235/T polymorphism of the AGT(angiotensinogen) gene by PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism) in 120 CHD patients and 80 control subjects. CHD patients who underwent coronary angiography were determined the number of affected coronary vessels( 75% stenosis) and coronary Jeopardy score and were inspected the risk factors of CHD. 1. Relationship between RAS gene polymorphisms and CHD 1.1 Association between ACE gene I/D polymorphism and CHD DD genotype and D allele were found more frequently in CHD patients than normal controls (31.7% of cases versus 16.3% of controls and 56% of cases versus 41% of controls, P<0.05). There was a significant increase in risk of CHD and MI(myocardial infarction) associated with the ACE-DD genotype, the OR(odds rations) were 2.388 (95%CI, 1.177-4.847) and 2.465 (95%CI, 1.128-5.386) respectively. The resultsuggested that the ACE-DD genotype and D allele were statistically associated with CHD and MI.1.2 Association between AT1R gene A1166/C polymorphism and CHD Twogenotype (AA and AC) of the AT1R gene were found, CC genotype was absent. The frequency of the AT1R-AC genotype and C allele did not differ between the patients and the controls(13.3% vs 10%, and 7% vs 5% respectively, P>0.05). There is no association between AT1R gene A1166/C polymorphism and the occurrence of CHD in Chinese people from Zhongyuan area. OR for risk of CHD and MI associated with AT1R-AC genotype were 1.385 (95%CI, 0.563-3.407) and 1.2(95%CI, 0.425-3.407) respectively.1.3 Association between AGT gene M235/T polymorphism and CHD There were no difference in either the distribution or allele frequencies between patients and controls for AGT gene polymorphism (P>0.05). The frequency of the AGT-TT genotype and T allele were 40%, 63% in patients and 32.5%, 59% in controls. Therefore no association was found between the M235/T polymorphism of AGT gene and CHD or MI. OR for risk of CHD and MI associated with AT1R-AC genotype were 1.518 (95%CI, 0.836-2.75) and 1.636 (95%CI, 0.834-3.21) respectively.1.4 Combined analysis of the association between ACE-I/D, AT1R-A1166/C and AGT-M235/T polymorphism and CHD There was no difference in genotype distribution between patients and controls bearing the combined DD and AC genotype. But a significant increase in risk of CHD (OR=4.89) and MI (OR=3.65) was found in patients carrying the combined DD and AC genotypes compared with the patients carrying the combined DD and AA genotypes and patients only with the ACE-DD genotype. These observations indicated the interaction between the two polymorphisms. AT1R-AC genotype increased the risk of CHD and MI associated with the ACE-DD genotype. The frequency of combined DD and TT genotypes was higher either in patients with CHD or inpatients with MI than controls (P<0.05). OR for risk of CHD and MI associated with the combined DD and TT genotypes were 6.44 and 8.36 respectively, which are significant higher than the OR associated with either only ACE-DD genotype or AGT-TT genotype. The evidence surpport theinteraction between ACE-I/D and AGT-M235/T polymorphisms. There was no evidence was found to support any interaction between AT1R-A1166/C and AGT-M235/T polymorphisms.2. Association between the RAS gene polymorphisms and the severity of coronary artery stenosis2.1 Association between the ACE-I/D gene polymorphism and the severity of coronary artery stenosis Neither the number of affected coronary vessels nor the coronary jeopardy score differed among the ACE I/D genotypes (P>0.05). The result suggest that the ACE-I/D gene polymorphism was not statistically associated wi...