Association Between A/C1166 Gene Polymorphism of the Angiotensin II Type 1 Receptor and Biventricular Functions in Patients With Acute Myocardial Infarction

Abstract

cute myocardial infarction (AMI) is characterized by loss of contractile tissue and changes in ventricular geometry. 1 The presence of congestive heart failure or left ventricular (LV) systolic dysfunction is probably the most important risk factor in patients with AMI. 2 The development of right ventricular (RV) dysfunction has been reported following LV myocardial infarction (MI), 3,4 and is also associated with increased risk of shock, arrhythmia, and death. 5,6 After MI, the process of LV remodeling begins rapidly, usually within the first few hours after an infarct, and continues to progress. 7 Furthermore, it is known that the renin -angiotensin -aldosterone system (RAS) and angiotensin-converting enzyme (ACE) activity contribute to the remodeling process. 8 Angiotensin II (ATII) is the final effector of the RAS. It is a vasoactive peptide and leads to growth promotion, fibroblast proliferation, and the most potent vasoactive and salt-retaining effector peptide of the RAS, which is involved in blood pressure homeostasis and cardiovascular pathophysiology. Two subtypes of cell surface receptors, ATII type 1 receptor (AT1R) and ATII type 2 receptor Circulation Journal Vol. 70, October 2006 (AT2R), have been identified. Most of the actions of ATII are mediated by AT1, which is particularly prominent in the myocardium. 9,10 Although a number of polymorphisms of the AT1R gene have been identified, one of the most widely studied is an A-C substitution at position 1166 (A/C1166). 11 Two-dimensional (D) and Doppler echocardiography is a reliable tool for the diagnosis of systolic and diastolic dysfunction. The Doppler echocardiographic myocardial performance index (MPI) called the "Tei index", combining time intervals of LV contraction and relaxation, has been shown to be a powerful predictor of death and congestive heart failure after MI. 12,13 This index can be obtained easily, is reproducible and independent of the ventricular geometry, and has been shown to have potential for clinical application in the assessment of overall cardiac function in various disorders. 14 Poulsen et al recently reported that the LVMPI was a powerful predictor of death or congestive heart failure after MI, 15 and Moller et al showed that the RVMPI was increased in the acute phase of MI and was significantly correlated with indices of RV systolic dysfunction. 16 In a previous study, we reported higher LVMPI and RVMPI in patients with the DD genotype than in patients with the ID genotype of the ACE gene after anterior AMI. 17 Although there have been several association studies of the polymorphism of AT1R (A/C1166) in clinical endpoints, such as MI, 18 hypertension, 11 aortic stiffness, 19 and LV mass, 20 to our knowledge the relationship between AT1R polymorphism and biventricular function in anterior Methods and ResultsThe study group comprised 132 consecutive patients who were admitted to the coronary care unit with their first acute anterior MI. Systolic and diastolic diameters, volumes, inflow properties, ejection fraction an...

Relation between AT1R Gene Polymorphism and Long-Term Outcome in Patients with Heart Failure

“…This allele distribution showed a similarity to the respective frequencies reported in the single nucleotide polymorphism database using different European Caucasian populations or samples of the Centre d’Etude du Polymorphisme Humain (65–75 and 25–35% for the A and C alleles, respectively). Considerable interethnic variation in the frequencies of this polymorphism has been demonstrated, with the –1166C allele being rarer in African American and Asian populations (94–97 and 3–6% for the A and C alleles, respectively, single nucleotide polymorphism database) compared with European Caucasian groups [20], which is consistent with our findings. …”

“…However, most studies did not find a role for the AT1R polymorphism in the determination of LV size and performance, both in healthy individuals and in patients with coronary artery disease [15,16,17,18,19,20]. Hamon et al [21] showed that subjects homozygous for the AT1R CC mutation did have a lower EF than those with at least a single A allele (AC + AA).…”

Association between Angiotensin II Type 1 Receptor Polymorphism and Sudden Cardiac Death in Myocardial Infarction

“…Some studies have reported a positive association [12–14], while others could not find any association [10, 11, 28, 29]. …”

Genetic Variations of Mrf-2/Arid5b Confer Risk of Coronary Atherosclerosis in the Japanese Population

“…24,25) A number of initial studies attempted to address the possibility that polymorphisms at various candidate genes might be associated with the pathogenesis of CAD and some concluded there was a significant association between them. For example, polymorphisms in renin-angiotensin system gene polymorphisms (angiotensin-type receptor genes, angiotensin II converting enzyme genes) are well known to be associated with hypertension, 26) CAD [27][28][29][30][31] and MI, [32][33][34] though dissenting opinions still exist.…”