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 geno-type 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 ε4 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 + APOE ε4 allele carriers. (C) 2000 American Association for Clinical Chemistry.