Association of 2 neurotrophic factor polymorphisms with efficacy of paroxetine in patients with major depressive disorder in a Chinese population.

Background: To evaluate the influence of the single nucleotide polymorphism (SNP) rs 6265 in the brain-derived neurotrophic factor (BDNF) gene and 21 SNPs of the glial cell line-derived neurotrophic factor (GDNF) gene on the efficacy of paroxetine in patients with major depressive disorder (MDD).

Methods: Genotyping for BDNF and GDNF polymorphisms was performed in 298 patients with MDD who started 20 mg paroxetine per day and had their plasma concentrations measured after 6 weeks. The SNPs were selected from the HapMap Chinese ethnic group and literature reports. Changes in the severity of MDD were assessed with the Hamilton Depression Rating Scale (HAM-D) at baseline and at a 6-week follow-up. Paroxetine plasma concentration was measured using high-performance liquid chromatography with fluorescence detection. The Sequenom MassArray system was used for genotyping.

Results: At the 6-week follow-up, 219 of the 298 patients (73.5%) were responders and 79 patients (26.5%) were nonresponders to paroxetine treatment. The lower threshold concentration of paroxetine for response was 50 ng/mL, and a linear relationship was found between paroxetine plasma concentration and clinical response. The allele types for the SNPs rs 6265 (P < 0.001), rs 2973049 (P = 0.005), and rs 2216711 (P = 0.006) demonstrated significant associations with paroxetine treatment remission at week 6.

Conclusions: Genetic variants in the BDNF and GDNF regions may be indicators of treatment response to paroxetine in patients with MDD.