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

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