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 825T allele of the G-protein ss(3)-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.
Naber
C K
CK
Abteilung für Kardiologie, Institut für Medizinische Informatik, Biometrie und Epidemiologie, Abteilung für Thorax- und Kardiovaskuläre Chirurgie, Universitätsklinikum Essen, Germany. christoph.naber@uni-essen.de
Hüsing
J
J
Wolfhard
U
U
Erbel
R
R
Siffert
W
W
D000368:Aged; D000483:Alleles; D000792:Angiography; D003327:Coronary Disease / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
D007703:Peptidyl-Dipeptidase A; D020962:Heterotrimeric GTP-Binding Proteins