Combined action of the ACE D- and the G-protein β3 T-allele in major depression : a possible link to cardiovascular disease?

• Published in: Molecular psychiatry Vol. 7; no. 10; pp. 1120 - 1126
• Main Authors: BONDY, B, BAGHAI, T. C, ZILL, P, BOTTLENDER, R, JAEGER, M, MINOV, C, SCHULE, C, ZWANZGER, P, RUPPRECHT, R, ENGEL, R. R
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-12-2002
• Subjects: Adult and adolescent clinical studies; Affective disorders; Alleles; Angiotensin; Angiotensin I; Biological and medical sciences; Cardiovascular disease; Cardiovascular diseases; Central nervous system; Cerebrovascular diseases; Coronary artery; Gene polymorphism; Heart diseases; Homozygotes; Medical sciences; Mental depression; Miscellaneous; Mood disorders; Myocardial infarction; Polymorphism; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Risk factors; Mood disorder; Human; Infarct; Enzyme; Pathogenesis; Cardiovascular disease; Depression; Coronary heart disease; Myocardial disease; Case study; Peptidases; Enzymatic activity; Peptidyl-dipeptidase A; Clinical biology; Myocardium; Mental disorder; Hydrolases; Peptidyl-dipeptidases; Complication; Genetics; Polymorphism; G protein
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4001149

Although it is well established that depression is a major risk factor for the development of coronary artery disease and that cerebrovascular disease can be a major contributing factor for the development of depression, the information about the interplay between the central nervous system and cardiovascular disease is still limited. We investigated the angiotensin I converting enzyme (ACE) ID and the G-protein β3-subunit (Gβ3) C825T polymorphism in 201 patients with unipolar major depression and 161 ethnically and age-matched controls. Both gene variants have earlier been associated with either cardiovascular disease or affective disorders, making them good candidates for a combined analysis. We found a significant increase in the Gβ3 T allele (OR = 1.61, 95% CI 1.17–2.2, P = 0.0035) and a marginal altered genotype distribution of the ACE ID polymorphism with decrease in the II genotypes (χ2 = 6.43, df=3, P = 0.04) in the patients’ group. Analysing the data for both genes we found that the combined actions of ACE and Gβ3 genotypes accumulate in carriers of the ACE D allele (ID and DD) and Gβ3 TT homozygotes with ID/DD-TT carriers showing a more than five-fold increase in risk for major depression (crude OR = 5.83, 95% CI 1.99–17.08, P = 0.0002). As our study was carried out with depressive patients without serious cardiac impairment at the time of the investigation, we are presently unable to predict whether this combined action of the ACE ID/DD–Gβ3 TT genotype is increasing the risk for both disorders. Nevertheless our study reports for the first time that the same allelic combination of two genes that have been shown to increase the risk for myocardial infarction (Naber et al, 2000) increase the vulnerability for depressive disorder.