An Association Study On Pharmacogenomics In BDNF Signal Pathways Of Major Depressive Disorder

Objective:To explore the association between gene polymorphisms in brain-derived neurotrophic factor (BDNF) signal pathway genes with the therapeutic efficacy and adverse drug reaction of citalopram in Chinese Han major depressive disorder (MDD) patients.Methods:A total of 78 MDD patients diagnosed by DSM-IV were treated with citalopram over 6 weeks and evaluated at week 1,2,4 and 6. The therapeutic efficacy was evaluated by the total scores of HAMD-17 and the reduction rate.The adverse drug reaction was evaluated by the scores of TESS. Polymerase chain reaction (PCR) and DNA sequencing were used to genotype 7 singal nucleotide polymorphisms (SNPs) of PKB, GSK3-β, PRKCG and BDNF genes in BDNF signal pathways. The SNPs including rs2494746, rs2494738 and rs3001371 in PKB gene, rs6782799 in GSK3-βgene, rs3745406 in PRKCG gene, rs6265 and rs7124442 in BDNF gene. The association analyses were performed by SPSS13.0 software.Results:1. Hardy-Weinberg equilibrium (HWE) testExcept PKB rs2494738, other 6 SNPs (rs2494746 and rs3001371 in PKB gene, rs6782799 in GSK3-βgene, rs3745406 in PRKCG gene, rs6265 and rs7124442 in BDNF gene) in this sample were in HWE (P>0.05), which indicated that the sample can represent the population.2. General demography data analysisThere were no significant differences in distributions of mean age, sex and educational background between different groups(P>0.05).3. Association analyses of SNPs with the efficacyA genotypic association between BDNF rs7124442 and the efficacy of citalopram was found in our sample (P=0.010,χ2=5.422), and the alle C carriers (CC+CT)showed a poorer response to antidepressive treatment with citalopram (OR=4.76). No associations of other SNPs were found in our Chinese Han MDD population.4. Association analyses of SNPs with the adverse drug reactionA genotypic association between PKB rs2494746 and the appearance of constipation was found in our sample (P=0.042,χ2=4.416), and the alle C carriers (CC+CG) showed a poorer possibility of constipation (OR=2.74). The genotype of PRKCG rs3745406 was associated with the appearance of nausea and vomiting (P=0.029,χ2=4.779), and the alle A carriers (AA+AG) showed a poorer possibility of nausea and vomiting (OR-5.45) Conclusions:1.BDNF rs7124442 may be associated with the efficacy of citalopram in Chinese Han MDD population.2. PKB and PRKCG SNPs may be associated with some adverse drug reaction of citalopram.