C825T polymorphism in the G protein beta3-subunit gene is associated with seasonal affective disorder

Heterotrimeric G proteins play a pivotal role in the intracellular transduction of many transmitter-receptor interactions. Alterations in signal transduction and in G protein concentrations have been reported in seasonal and nonseasonal affective disorder. A single-nucleotide polymorphism (C825T) in the G protein beta3-subunit gene has been shown to influence intracellular response to G protein-coupled stimuli, and the T-allele of this polymorphism has been associated with hypertension and major depression.

We genotyped deoxyribonucleic acid from peripheral mononuclear cells of 172 patients with seasonal affective disorder, winter type (SAD), and 143 healthy control subjects.

Patients with SAD were significantly more likely to be either homo- or heterozygous for the G(beta)3 T-allele when compared with healthy control subjects (p =.001), and they displayed a higher frequency of the G(beta)3 C825T T-allele (p =.021). The polymorphism was not associated with seasonality, which is the tendency to experience variations in mood and behavior with changing of the seasons.

The G(beta)3 C825T polymorphism was associated with SAD in our study sample. This finding strengthens the evidence for the involvement of G protein-coupled signal transduction in the pathogenesis of affective disorder.