Renin-angiotensin-aldosterone system gene polymorphisms and coronary artery disease: detection of gene-gene and gene-environment interactions.
Abstract | OBJECTIVE: The objective of this study was to explore the association between coronary artery disease and genetic polymorphisms of the renin-angiotensin-aldosterone system (RAAS) pathway. In addition, we examined the interactions between demographic and lifestyle risk factors (environmental factors including age, sex, smoking status, alcohol intake) and RAAS polymorphisms on disease risk. METHODS: RESULTS: Compared to the subjects with AA genotype, the subjects with AG + GG genotype of rs1799998 had significant lower gensini score (p=0.029). After adjusting for age, gender, cigarette smoking, and alcohol intake status, the AG genotype (OR 0.717 95%CI 0.541-0.950, p=0.021) and the AG + GG genotype (OR 0.730 95%CI 0.559-0.954, p=0.021) distributions of rs1799998 were significantly different between the cases and controls compare to the AA genotype. Subjects with three at-risk loci had increased risk of coronary artery disease compared to subjects carrying 0 or 1 risk-associated polymorphism (OR [95% CI]:1.579 [1.077-2.316], p=0. 019), and the significance of the association was not reduced after adjusting for age, sex, cigarette smoking, or alcohol intake (adjusted OR [95% CI]: 1.673 [1.116-2.507], p=0.013). The results of multifactor-dimensionality reduction analysis revealed an interaction effect of CYP11B2 -344C→T, age, and smoking status on the risk of coronary heart disease (training OR [95% CI]: 3.7685 [2.8463-4.9895], p<0.0001; testing OR [95% CI]: 2.7583 [1.2038-6.3203], p=0.015). CONCLUSIONS:
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Authors | En-Zhi Jia, Zhen-Xia Xu, Chang-Yan Guo, Li Li, Yan Gu, Tie-Bing Zhu, Lian-Sheng Wang, Ke-Jiang Cao, Wen-Zhu Ma, Zhi-Jian Yang |
Journal | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
(Cell Physiol Biochem)
Vol. 29
Issue 3-4
Pg. 443-52
( 2012)
ISSN: 1421-9778 [Electronic] Germany |
PMID | 22508051
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 S. Karger AG, Basel. |
Chemical References |
- AGT protein, human
- AGTR1 protein, human
- Receptor, Angiotensin, Type 1
- Angiotensinogen
- Cytochrome P-450 CYP11B2
- ACE protein, human
- Peptidyl-Dipeptidase A
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Topics |
- Age Factors
- Aged
- Alcoholism
(pathology)
- Alleles
- Angiotensinogen
(genetics)
- Case-Control Studies
- Coronary Angiography
- Coronary Artery Disease
(genetics, pathology)
- Cytochrome P-450 CYP11B2
(genetics)
- Epistasis, Genetic
- Exons
- Female
- Gene-Environment Interaction
- Genetic Loci
- Genotype
- Humans
- Life Style
- Male
- Middle Aged
- Odds Ratio
- Peptidyl-Dipeptidase A
(genetics)
- Polymorphism, Genetic
- Receptor, Angiotensin, Type 1
(genetics)
- Renin-Angiotensin System
(genetics)
- Risk Factors
- Smoking
(adverse effects)
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