Synergistic Effect between Apolipoprotein E and Angiotensinogen Gene Polymorphisms in the Risk for Early Myocardial Infarction

Abstract

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 (ε2, ε3, and ε4 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 APOEε4 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 ε4 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 ε34/44 patients than in the TM/MM + ε34/44 or TT + ε23/33 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 + APOEε4 allele carriers.

Association between Apolipoprotein E polymorphism and myocardial infarction risk: A systematic review and meta‐analysis

“…Based on the search strategy, 571 potentially eligible studies were identified in the initial search. Among these, 22 studies were enrolled in this meta-analysis based on the inclusion criteria [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] ( Fig. 1 ).…”

Overestimation of genetic risks owing to small sample sizes in cardiovascular studies

“…We conducted systematic reviews of all published studies, abstracts, and letters to the editor, investigating the potential associations between three polymorphisms (ACE D, glycoprotein III PLA2, and F5L) and relevant cardiovascular outcomes. We searched medline (from 1990 to February 2001), and the bibliographies of research reports and meta‐analyses, in order to identify all eligible published studies of PLA2 (13–40), ACE D (8, 41–79), and F5L (80–101). We performed manual searches for additional relevant abstracts from cardiovascular genetic conferences.…”

Renin-Angiotensin System and Atherothrombotic Disease

“…In contrast, other studies 67,69 did not show any synergistic interactions. Results of a recent study 70 indicate a synergistic effect between AGT M235T and apolipoprotein E4, with increased risk of MI observed in AGT TT and apolipoprotein E4 carriers.…”