(Hypertension. 2000;36:986.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Interaction of the ACE D Allele and the GNB3 825T Allele in Myocardial Infarction
From the Abteilung für Kardiologie (C.N., R.E.), Institut für Medizinische Informatik, Biometrie und Epidemiologie (J.H.), Institut für Pharmakologie (W.S.), Abteilung für Thorax- und Kardiovaskuläre Chirurgie (U.W.), Universitätsklinikum Essen (Germany).
Correspondence to Christoph K. Naber, MD, Abteilung für Kardiologie, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany. E-mail christoph.naber{at}uni-essen.de
Abstract—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 825T allele of the G-protein ß3-subunit gene (GNB3) associated with enhanced G-protein signaling is a candidate to interact with the angiotensin-converting enzyme (ACE) deletion/insertion (D/I) polymorphism to increase the risk for myocardial infarction (MI). The ACE D/I variant affects the renin-angiotensin system hormones that activate G-protein–coupled receptors. Genotyping at the ACE and GNB3 loci was performed on 585 patients with coronary artery disease with (n=270) or without (n=315) previous MI. Logistic regression analysis demonstrated a significant interaction between the ACE D allele 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 genotype (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 individuals with the ACE DD genotype (OR 2.4; P=0.02). The highest odds ratio was found 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.
Key Words: myocardial infarction • genetics • signal transduction • G proteins • angiotensin-converting enzyme
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