Evidence for an association between a G-protein β3-gene... : NeuroReport (original) (raw)

GENETICS OF NERVOUS SYSTEM DISEASES

Evidence for an association between a G-protein β3-gene variant with depression and response to antidepressant treatment

Zill, Peter1,2; Baghai, Thomas C.1; Zwanzger, Peter1; Schüle, Cornelius1; Minov, Christo1; Riedel, Michael1; Neumeier, Karin1; Rupprecht, Rainer1; Bondy, Brigitta1

1Psychiatric Hospital of the Ludwig-Maximilians-University, Nussbaumstr. 7, D-80336 Munich, Germany

2Corresponding Author: Peter Zill

Acknowledgements: This project is supported by the German Federal Research Ministry within the promotional emphasis ‘Competence Nets in Medicine’.

Received 15 March 2000; accepted 31 March 2000

Abstract

Abnormal signal transduction pathways have been implicated in the pathogenesis of bipolar disorder and major depression. G-proteins are key elements of these pathways in the regulation of cellular responses by transmission of signals from receptors to effector proteins. In recent years several studies have reported altered levels and activities of G-protein α subunits in depressive patients. A recently identified polymorphism of a G-protein β3 subunit (C825T) has been shown to be associated with increased signal transduction and ion transport activity. Therefore, we investigated whether this Gβ3 polymorphism is associated with affective disorders or with the response to antidepressant treatment in 88 depressive patients (10 bipolar disorder, 78 major depression) compared with 68 schizophrenic patients and 111 healthy controls. We found a significantly higher frequency of the T allele in depressive patients than in healthy controls (genotype: X2 = 9.571, df = 2, p = 0.008; alleles: p = 0.004, OR = 1.87, 95% CI 1.23–2.84; Fisher's exact test, two sided) and schizophrenic patients (genotype: X2 = 8.037, df = 2, p = 0.018; alleles: p = 0.009, OR = 1.94, 95% CI 1.99–3.14; Fisher's exact test, two sided). We also found a statistical significant association between TT homozygosity and response to antidepressant treatment after four weeks (p = 0.01). The results of this study suggest that the investigated G-protein β3 subunit seems to be a susceptibility factor for major depression and maybe even for bipolar disorder, but not for schizophrenia. Further, the presence of the T allele could be an indicator for treatment response.