Association of 2 Neurotrophic Factor Polymorphisms With Efficacy of Paroxetine in Patients With Major Depressive Disorder in a Chinese Population

Abstract

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