Purpose: Heterotrimeric guanine nucleotide-binding proteins (G proteins) are a major group of human genome membrane protein receptors. Genetic variation in the β3 subunit (GNβ3) associated with gene splicing and increased activity is associated with major depressive disorder (MDD). However, the effect of G-350A GNβ3 genetic polymorphism and therapeutic outcome of selective serotonin reuptake inhibitors (SSRIs) in MDD has not yet been studied.
Method: One hundred newly diagnosed MDD patients were treated with sertraline for 6 weeks. The severity of depressive symptoms was weekly assessed by Hamilton Rating Scale for Depression (HRSD). A 50% decrease in HRSD was defined as response to treatment. GNβ3 polymorphisms (G-350A, A657T) were determined in each individual using a PCR-RFLP technique.
Results: Our results suggested that subjects with GG genotype of G-350A responded 5.9-folds more to sertraline compared to carriers of other variants (P = 0.004, OR = 5.9; 95% CI = 1.66-21.99). In addition, carriers of the G allele responded 1.9-folds more to sertraline than carriers of the A allele (P = 0.032, OR = 1.92; 95% CI = 1.05-3.65). However, no association was observed between A657T variants and response to sertraline (P = 0.920, OR = 0.9; 95% CI = 0.31-2.69).
Conclusion: The results suggest that G-350A variant of GNβ3 plays a foremost part as a predictor of response to antidepressant treatment.
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