P. Zill et al., Evidence for an association between a G-protein beta 3-gene variant with depression and response to antidepressant treatment, NEUROREPORT, 11(9), 2000, pp. 1893-1897
Abnormal signal transduction pathways have been implicated in the pathogene
sis of bipolar disorder and major depression. G-proteins are key elements o
f these pathways in the regulation of cellular responses by transmission of
signals from receptors to effector proteins. in recent years several studi
es have reported altered levels and activities of C-protein ct subunits in
depressive patients. A recently identified polymorphism of a G-protein beta
3 subunit (C825T) has been shown to be associated with increased signal tr
ansduction and ion transport activity. Therefore, we investigated whether t
his G beta 3 polymorphism is associated with affective disorders or with th
e response to antidepressant treatment in 88 depressive patients (10 bipola
r disorder, 78 major depression) compared with 68 schizophrenic patients an
d 111 healthy controls. We found a significantly higher frequency of the T
allele in depressive patients than in healthy controls (genotype: chi(2)=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: chi(2) = 8.
037, df = 2, p = 0.018; alleles: P = 0.009, OR = 1.94, 95% Ct 1.99-3.14; Fi
sher's exact test, two sided). We also found a statistical significant asso
ciation between TT homozygosity and response to antidepressant treatment af
ter four weeks (P=0.01). The results of this study suggest that the investi
gated G-protein beta 3 subunit seems to be a susceptibility factor for majo
r 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. NeuroReport 11:1893-1897 (C) 2000 Lippincott Williams & Wilkins.