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Renin-angiotensin system polymorphisms and coronary events in familial hypercholesterolemia
A S Wierzbicki1, M Lambert-Hammill, P J Lumb
1Lipid Unit, Department of Chemical Pathology, King's College, London.
Insights
The angiotensin-II type I receptor A1166C polymorphism is a risk factor for coronary heart disease (CHD) in familial hypercholesterolemia (FH) patients. This genetic factor, along with others, increases CHD risk in FH individuals.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Pharmacogenomics
Background:
- The role of renin-angiotensin system (RAS) gene polymorphisms in coronary heart disease (CHD) remains debated.
- Familial hypercholesterolemia (FH) is a genetic condition leading to high cholesterol and increased cardiovascular risk.
Purpose of the Study:
- To investigate the association between specific RAS polymorphisms and CHD risk in patients with heterozygous FH.
- To identify independent risk factors for CHD in FH patients.
Main Methods:
- Genotyping for angiotensin-I-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T, and angiotensin-II type I receptor (AGTR1) A1166C polymorphisms.
- Analysis of polymorphism frequencies in 112 FH patients and 72 polygenic hypercholesterolemia patients.
- Logistic regression analysis to determine CHD risk factors in FH patients.
Main Results:
- No significant association was found between the studied RAS polymorphisms and CHD risk in polygenic hypercholesterolemia patients.
- In FH patients, male sex, smoking, diastolic blood pressure, plasma glucose, and the AGTR1 A1166C polymorphism were identified as risk factors for CHD.
- The AGTR1 A1166C polymorphism showed an increased odds ratio for CHD in FH patients, particularly after adjusting for other risk factors.
Conclusions:
- The AGTR1 A1166C polymorphism may contribute to increased CHD risk in FH patients.
- This genetic risk factor might interact with severe hypercholesterolemia and other traditional risk factors to exacerbate CHD development in FH individuals.
Abstract:
The role of renin-angiotensin system polymorphisms as risk factors for coronary heart disease (CHD) is controversial. This study investigated their role in patients with heterozygous familial hypercholesterolemia (FH). Polymorphism frequencies for angiotensin-I-converting enzyme insertion/deletion (ACE I/D), angiotensinogen M235T, and angiotensin-II type I receptor (AG2R) A1166C were determined in 112 patients with FH and 72 patients with polygenic hypercholesterolemia, of whom 26.7% and 41.6%, respectively, had established CHD. None of the polymorphisms were associated with risk of CHD in patients with polygenic hypercholesterolemia in this study. Logistic regression analysis of risk factors for CHD in patients with FH identified male sex (odds ratio [OR]=3.03; 95% CI, 3.07 to 3.72; P=0.05), smoking (OR=2.91; 95% CI, 2.16 to 4.24; P=0.05), diastolic blood pressure (OR=3.70; 95% CI, 3.43 to 3.97; P=0.02), plasma glucose (OR=3.31; 95% CI, 3. 10 to 3.52; P=0.04), and the AG2R A1166C polymorphism as risk factors. The OR for the AG2R A1166C polymorphism was 2.26 (95% CI, 1.26 to 3.72; P=0.06) and increased to 3.10 (95% CI, 1.20 to 7.52; P=0.04) after adjustment for other risk factors. The AG2R A1166C polymorphism may interact with severe hypercholesterolemia and other risk factors to increase risk of CHD in FH patients.