Synergistic Effect Between Apolipoprotein E and Angiotensinogen Gene Polymorphisms in the Risk for Early Myocardial Infarction (Molecular Diagnostics and Genetics‪)‬

Apolipoprotein E (ApoE) [5] is a plasma protein involved in cholesterol transport. ApoE is encoded by a polymorphic gene on chromosome 19 (the APOE gene), and three alleles ([member of]2, [member of]3, and [member of]4) have been described. These alleles differ in the amino acids at residues 112 (Cys in [member of]3 and [member of]2, and Arg in [member of]4) and 158 (Arg in [member of]3, Cys in [member of]2, and Arg in [member of]4) (1,2). The APOE [member of]4 allele is a well-recognized risk factor for Alzheimer disease, and several case-control studies have described an increased risk for coronary artery disease (CAD) among [member of]4 carriers, with [member of]44 homozygotes showing an earlier onset of the disease (3-10). However, other authors have found a nonsignificantly increased or even a decreased frequency of the [member of]4 allele among CAD patients (11, 12). Compared with [member of]33 homozygotes, carriers of the [member of]2 and [member of]4 alleles showed decreased and increased LDL-cholesterol, respectively (13). The [member of]2 allele has also been associated with higher triglyceride concentrations (14). DNA polymorphisms in the angiotensinogen (AGT), angiotensin receptor type 1 (ATM), and angiotensin' converting enzyme (ACE) genes have been linked to the risk of developing cardiovascular diseases. Among these polymorphisms, the ACE insertion/ deletion (I/D) and the AGT-235M/T polymorphisms have been linked with differences in ACE and angiotensin II (Ang II) concentrations in plasma. Compared with individuals with an ACE-ID/II or AGT-MM/TM genotype, ACE-DD and AGT-TT genotypes have significantly higher concentrations of ACE and angiotensin, respectively (15,16). The ACE-DD and AGT-TT genotypes have been associated with an increased risk for CAD in some studies, but not others (17-19). Several metaanalyses have investigated the association of the ACE polymorphism with myocardial infarction (MI). Whereas some authors found evidence for an association between the DD genotype and MI, others failed to confirm this result and suggested a bias toward publishing positive associations (20-22).