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Multilocus analysis in candidate genes ACE, AGT, and AGTR1 and predisposition to peripheral arterial disease: role of ACE D/-240T haplotype.
- Source :
-
Journal of vascular surgery [J Vasc Surg] 2009 Dec; Vol. 50 (6), pp. 1399-404. Date of Electronic Publication: 2009 Sep 26. - Publication Year :
- 2009
-
Abstract
- Objective: Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis. Apart from traditional cardiovascular risk factors, several novel biologic mediators and genetic predisposing factors appear relevant in determining the atherogenetic process leading to PAD. Genes encoding for renin angiotensin system (RAS) components have been proposed as candidate in atherosclerosis. This study investigated four polymorphisms in angiotensinogen (AGT), angiotensin converting enzyme (ACE), and angiotensin II receptor type 1 (AGTR1), genes of RAS, in both predicting PAD and modulating the severity of the disease.<br />Methods: The ACE I/D and -240A>T, AGT M235T, and AGTR1 1166A>C polymorphisms were analyzed in 281 PAD patients and in 485 controls comparable for age and sex.<br />Results: The ACE D and -240T alleles both significantly influenced the predisposition to PAD. The ACE D, but not -240 T, allele remained associated with PAD after Bonferroni correction (P = .004) and adjustment for cardiovascular risk factors (P = .03). The ACE D allele influenced PAD predisposition with a dose-dependent effect (odds ratio for ACE ID vs II genotype, 1.77; P = .006; ACE DD vs II genotype, 2.15; P = .001). The haplotype reconstruction analysis for the ACE gene showed that the D/-240T haplotype significantly and independently influenced the predisposition to PAD (P = .02). In 190 PAD patients with no additional atherosclerotic localizations (isolated PAD), a significant association between ACE D and -240T alleles and PAD was observed. Only the ACE D allele remained associated with isolated PAD after Bonferroni correction (P = .02) and after adjustment for cardiovascular risk factors (P = .02). The haplotype reconstruction analysis for the ACE gene showed that the D/-240T, but not the D/-240A haplotype significantly influenced the predisposition to PAD (P = .0003). No influence of the polymorphisms analyzed on the severity of the disease, according to Rutherford categories, was found.<br />Conclusions: The present study contributes data to highlight the role of the ACED/-240T haplotype in predisposing to PAD, also in the absence of other atherosclerotic comorbidities.
- Subjects :
- Adult
Aged
Aged, 80 and over
Case-Control Studies
Female
Gene Frequency
Genetic Predisposition to Disease
Haplotypes
Humans
Logistic Models
Male
Middle Aged
Odds Ratio
Peripheral Vascular Diseases enzymology
Phenotype
Risk Assessment
Risk Factors
Severity of Illness Index
Angiotensinogen genetics
Peptidyl-Dipeptidase A genetics
Peripheral Vascular Diseases genetics
Polymorphism, Genetic
Receptor, Angiotensin, Type 1 genetics
Renin-Angiotensin System genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6809
- Volume :
- 50
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of vascular surgery
- Publication Type :
- Academic Journal
- Accession number :
- 19782519
- Full Text :
- https://doi.org/10.1016/j.jvs.2009.07.075