Synergistic effect between apolipoprotein E and angiotensinogen gene polymorphisms in the risk for early myocardial infarction

Background: Several studies based on different populations worldwide have d escribed an association between cardiovascular diseases and genetic variati ons in the apolipoprotein E (APOE), angiotensinogen (AGT), angiotensin rece ptor type 1 (AT1R), and angiotensin-converting enzyme (ACE) genes. In addit ion, there is growing evidence of an interaction between hypercholesterolem ia and the renin-angiotensin system in the risk for hypertension and athero sclerosis. Methods: To determine whether the DNA polymorphisms in APOE (epsilon2, epsi lon3, and epsilon4 alleles), AGT (M235T), AT1R (1166 A/C), and ACE (I/D) ar e associated with early onset of myocardial infarction (MI), we genotyped 2 20 patients and 200 controls <55 years of age. Patients and controls were m ales from the same homogeneous Caucasian population. Data concerning hypert ension, 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 d iffer between patients and controls. None of these polymorphisms was relate d to the biochemical values in patients or controls. The frequency of indiv iduals who were both APOE <epsilon>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 epsilon4 carriers was significantly hi gher (P < 0.00001) in those who were AGT-TT (46%) than those who were AGT-M T/MM (14%). Mean cholesterol was significantly higher in AGT-TT + APOE <eps ilon>34/44 patients than in the TM/MM + 34/44 or TT + epsilon 23/33 genotyp es (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 t hrough higher cholesterol concentrations among individuals who are AGT-TT APOE epsilon4 allele carriers. (C) 2000 American Association for Clinical Chemistry.