文拉法辛临床疗效与γ-氨基丁酸β2受体基因的相关分析

Association Study of GABRB2 gene and antidepressant response to SNRI in patients with major depression.

目的探索γ-氨基丁酸β2受体(GABRB2)基因多态性与五羟色胺-去甲肾上腺素重吸收抑制剂(Serotonin and Norepinephrine Reuptake Inhibitor,SNRI)文拉法辛抗抑郁疗效差异的相关性。方法对151例抑郁症患者采用文拉法辛治疗6周,以治疗后17项汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)总分≤7为临床痊愈。检测5号染色体上的GABRB2基因的29个标签单核苷酸多态性(Single Nucleotide Polymorphisms,SNP)位点。运用Plink 1.07和Haploview4.2软件进行29个SNP位点及其构成的单倍型与药物疗效的相关分析。结果 GABRB2基因的rs10071312和rs4426954位点的等位基因频率在痊愈组和非痊愈组之间的差异有统计学意义(均P=0.02),rs10071312位点的A等位基因携带者的治疗痊愈率高于G等位基因携带者(OR=4.43),而rs4426954位点的A等位基因携带者的治疗痊愈率低于G等位基因携带者(OR=0.44)。有3种单倍型在痊愈组和非痊愈组之间的分布差异有统计学意义,分别是A-A-A-A-G-A(rs7724146-rs10051667-rs2964773-rs12153421-rs2962402-rs4426954,P=0.01),A-A-A-G-A(rs10051667-rs2964773-rs12153421-rs2962402-rs442695,P=0.02)和A-A-A-G-A-G(rs10051667-rs2964773-rs12153421-rs2962402-rs4426954-rs3816596,P=0.03)。结论 GABRB2基因多态性可能与文拉法辛治疗的个体化差异有关联。

Objective Gamma-aminobutyric acid（GABA） has been proved to play important roles in both the pathogenesis of depression and the outcome of antidepressant treatment.GABRB2 encodes one of the subunits consisting GABA receptor A.To investigate whether the Gamma-aminobutyric acid receptor subunit beta-2（GABRB2） gene polymorphisms is associated with the therapeutic response to venlafaxine,Serotonin and Norepinephrine Reuptake Inhibitor（SNRI） in major depressive disorder patients.Methods The study sample consisted of 151 patients with major depressive disorder.Patients with the scores of 17-Hamilton Rating Scale for Depression of depression（HAMD-17）≥18 were received antidepressants treatment（SNRI） for 6 weeks.HAMD-17 was ascertained before and after treatment.Individuals with HAMD≤7 after 6 weeks treatment were defined as remission.Using data in HapMap project,29 Single Nucleotide Polymorphisms（SNPs） of GABRB2 gene were selected.SNPs variations and association analysis were investigated using Illumina technology and Plink software,respectively.Results Genotype analysis in remissions and non-remissions after 6 weeks of antidepressant treatment showed that two SNPs of GABRB2 gene were associated with the antidepressant response to SNRI,rs10071312（P=0.02） and rs4426954（P=0.02）,after Bonferroni Correction respectively.A allele carriers of rs10071312 had more opportunities than G allele carriers for remission（OR=4.43） whereas G allele carriers of rs4426954 had more opportunities than A allele carriers for remission（OR=0.44）.Three haplotypes were associated with antidepressant therapeutic response in haplotype analyses including A-A-A-A-G-A（rs7724146-rs10051667-rs2964773-rs12153421-rs2962402-rs4426954,P=0.01）,A-A-A-G-A（rs10051667-rs2964773-rs12153421-rs2962402-rs442695,P=0.02） and A-A-A-G-A-G（rs10051667-rs2964773-rs12153421-rs2962402-rs4426954-rs3816596,P=0.03）.Conclusions The findings show that GABRB2 genetic variants may play a role in therapeutic response to venlafaxine.