Interaction of the ACE D allele and the GNB3 825T allele in myocardial infarction

In polygenetic disorders, such as ischemic heart disease, the investigation of gene-gene interactions rather than determination of single gene effects is crucial to better understand the contribution of genetic factors. The 8 25T allele of the G-protein beta (3)-subunit gene (GNB3) associated with en hanced G-protein signaling is a candidate to interact with the aniotensin-c onverting enzyme (ACE) deletion/insertion (D/I) polymorphism to increase th e risk for myocardial infarction (MI). The ACE D/I variant affects the reni n-angiotensin system hormones that activate G-protein-coupled receptors. Ge notyping at the ACE and GNB3 loci was performed on 585 patients with corona ry artery disease with (n=270) or without (n=315) previous MI. Logistic reg ression analysis demonstrated a significant interaction between the ACE D a llele and the GNB3 825T allele (P<0.001). The odds ratio for MI, associated with the 825T allele, was not increased in the presence of the ACE II geno type (OR 0.5; P=0.09) but was significantly higher in 825T allele carriers with the ACE DI genotype (OR 1.9; P=0.01) and further increased in individu als with the ACE DD genotype (OR 2.4; P=0.02). The highest odds ratio was f ound in homozygous 825T allele carriers with the ACE DD genotype (OR 7.5; P =0.006). Our data suggest a significant interaction of the GNB3 825T allele with the ACE D allele in MI. These hypothesis-generating data may justify larger prospective studies.