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Articles |
1
Servicio Cardiología, Hospital de Cabueñes, 33280 Gijón, Spain.
2
Laboratorio Genética Molecular-Instituto
Investigación Nefrológica and
3
Servicio
Cardiología, Hospital Central de Asturias, 33006 Oviedo, Spain.
4
Servicio Medicina Interna, Hospital Monte Naranco,
E-33006 Oviedo, Spain.
a Author for correspondence. Fax 34-985-273657; e-mail
ecoto{at}hcas.Insalud.es
Background: Several studies based on different populations worldwide have described an association between cardiovascular diseases and genetic variations in the apolipoprotein E (APOE), angiotensinogen (AGT), angiotensin receptor type 1 (AT1R), and angiotensin-converting enzyme (ACE) genes. In addition, there is growing evidence of an interaction between hypercholesterolemia and the renin-angiotensin system in the risk for hypertension and atherosclerosis.
Methods: To determine whether the DNA polymorphisms in
APOE (
2,
3, and
4 alleles), AGT
(M235T), AT1R (1166 A/C),
and ACE (I/D) are
associated with early onset of myocardial infarction (MI), we genotyped
220 patients and 200 controls <55 years of age. Patients and controls
were males from the same homogeneous Caucasian population. Data
concerning hypertension, diabetes, and tobacco consumption were
recorded. The lipid profiles of patients and controls were also
determined.
Results: APOE, ACE,
AGT, and AT1R allele and genotype
frequencies did not differ between patients and controls. None of these
polymorphisms was related to the biochemical values in patients
or controls. The frequency of individuals who were both
APOE 4 allele carriers
and AGT-TT homozygotes was significantly higher in
patients than in controls (11% vs 3.5%; P =
0.0037). In patients, the frequency of
4 carriers was significantly higher
(P <0.00001) in those who were AGT-TT
(46%) than those who were AGT-MT/MM
(14%). Mean cholesterol was significantly higher in
AGT-TT + APOE
34/44 patients than in the
TM/MM +
34/44 or
TT + 23/33 genotypes
(P = 0.029).
Conclusions: Our data suggest a synergistic effect between the
APOE and AGT polymorphisms and early MI.
The increased risk could be mediated in part through higher cholesterol
concentrations among individuals who are AGT-TT +
APOE 4 allele
carriers.
The following articles in journals at HighWire Press have cited this article:
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  E. Zintzaras, G. Raman, G. Kitsios, and J. Lau Angiotensin-Converting Enzyme Insertion/Deletion Gene Polymorphic Variant as a Marker of Coronary Artery Disease: A Meta-analysis Arch Intern Med, May 26, 2008; 168(10): 1077 - 1089. [Abstract] [Full Text] [PDF]
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 A. M. Bennet, E. Di Angelantonio, Z. Ye, F. Wensley, A. Dahlin, A. Ahlbom, B. Keavney, R. Collins, B. Wiman, U. de Faire, et al. Association of Apolipoprotein E Genotypes With Lipid Levels and Coronary Risk JAMA, September 19, 2007; 298(11): 1300 - 1311. [Abstract] [Full Text] [PDF]
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 M.-Q. Xu, Z. Ye, F. B. Hu, and L. He Quantitative Assessment of the Effect of Angiotensinogen Gene Polymorphisms on the Risk of Coronary Heart Disease Circulation, September 18, 2007; 116(12): 1356 - 1366. [Abstract] [Full Text] [PDF]
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 E. E. Ntzani, E. C. Rizos, and J. P. A. Ioannidis Genetic Effects versus Bias for Candidate Polymorphisms in Myocardial Infarction: Case Study and Overview of Large-Scale Evidence Am. J. Epidemiol., May 1, 2007; 165(9): 973 - 984. [Abstract] [Full Text] [PDF]
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 C. Sekuri, F S. Cam, E. Ercan, I. Tengiz, A. Sagcan, E. Eser, A. Berdeli, and M. Akin Renin-angiotensin system gene polymorphisms and premature coronary heart disease Journal of Renin-Angiotensin-Aldosterone System, March 1, 2005; 6(1): 38 - 42. [Abstract] [PDF]
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 Y. Song, M. J. Stampfer, and S. Liu Meta-Analysis: Apolipoprotein E Genotypes and Risk for Coronary Heart Disease Ann Intern Med, July 20, 2004; 141(2): 137 - 147. [Abstract] [Full Text] [PDF]
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G. H. Gibbons, C. C. Liew, M. O. Goodarzi, J. I. Rotter, W. A. Hsueh, H. M. Siragy, R. Pratt, and V. J. Dzau Genetic Markers: Progress and Potential for Cardiovascular Disease Circulation, June 29, 2004; 109(25_suppl_1): IV-47 - IV-58. [Full Text] [PDF]
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D. S. Jacoby and D. J. Rader Renin-Angiotensin System and Atherothrombotic Disease: From Genes to Treatment Arch Intern Med, May 26, 2003; 163(10): 1155 - 1164. [Abstract] [Full Text] [PDF]
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 G. Kolovou, D. Daskalova, and D. P. Mikhailidis Apolipoprotein E Polymorphism and Atherosclerosis Angiology, January 1, 2003; 54(1): 59 - 71. [Abstract] [PDF]
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 F. Somogyvari, Z. Szolnoki, J. Marki-Zay, and L. Fodor Real-Time PCR Assay with Fluorescent Hybridization Probes for Exact and Rapid Genotyping of the Angiotensin-converting Enzyme Gene Insertion/Deletion Polymorphism Clin. Chem., September 1, 2001; 47(9): 1728 - 1729. [Full Text] [PDF]
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