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

Abstract

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.

• Authors: Xin-Chen Wang, Du-Juan Xu, Gui-Hai Chen, Quan Xia, Li-Na Liu
• Journal: Therapeutic drug monitoring (Ther Drug Monit) Vol. 36 Issue 5 Pg. 612-7 (Oct 2014) ISSN: 1536-3694 [Electronic] United States
• PMID: 24577123 (Publication Type: Journal Article)

Chemical References

• Brain-Derived Neurotrophic Factor
• Glial Cell Line-Derived Neurotrophic Factor
• Serotonin Uptake Inhibitors
• Paroxetine

Topics

• Adult
• Asian People
• Brain-Derived Neurotrophic Factor (genetics, metabolism)
• Depressive Disorder, Major (drug therapy, genetics)
• Female
• Genotype
• Glial Cell Line-Derived Neurotrophic Factor (genetics, metabolism)
• Humans
• Male
• Middle Aged
• Paroxetine (blood, therapeutic use)
• Polymorphism, Single Nucleotide
• Selective Serotonin Reuptake Inhibitors (blood, therapeutic use)