Influence and interaction of genetic polymorphisms in norepinephrine transporter and enviroment on antidepressant drug response

Abstract

Objective To determine how genetic polymorphisms in norepinephrine transporter(NET) gene influence the response of antidepressant treatment and how they interact with childhood trauma and recent life stress in a Chinese depressive patients. Methods 281 Chinese Han depressive patients received single antidepressant drugs for 6 weeks. Hamilton Depression Scale-17 (HAMD-17), the Childhood Trauma Questionnaire short term (CTQ-SF) and the Life Events Scale (LES) were used to evaluate severity of depressive symptoms and the occurrence of stressful life events respectively. Three single nucleotide polymorphisms (SNPs) in norepinephrine transporter were genotyped. Associations of single locus and haplotypes with antidepressant treatment response were analyzed using UNPHASED 3.0.13. The interaction of gene and life stress was analyzed by SPSS13.0 software. Results One NET SNP rs2242446 was significantly associated with antidepressant response in this Chinese male sample(0.4118 vs 0.2375, χ2= 7.046, P=0.0079, OR=0.445, 95%CI(0.243-0.815)), as was the haplotype C-G(rs2242446 and rs5569; χ2=5.886, P=0.0153, OR=0.457, 95%CI(0.198-1.054)) and another haplotype C-G-G(rs2242446, rs1532701 and rs5569; χ2=5.360, P=0.0206, OR=0.530, 95%CI(0.202-1.386)) of NET in male samples. The NET SNPs rs5569 demonstrated interaction with childhood trauma to influence antidepressant response(β=-2.727, SE=1.195, P=0.023, OR=0.065, 95%CI(0.006-0.681)). Conclusion Antidepressant drug response was influenced by not only NET genetic polymorphisms in norepinephrine transporter gene but also interaction between the NET genetic polymorphisms and early life stress. Key words: Antidepressant drugs; Gene; Environment; Norepinephrine transporter