多巴胺β羟化酶和去甲肾上腺素转运体基因多态性与惊恐障碍的关联分析

Association analysis of the polymorphisms of dopamine-β-hydroxylase and norepinephrine transporter genes with panic disorder

目的:探讨惊恐障碍与多巴胺β羟化酶(dopamine-β-hydroxylase,DβH)和去甲肾上腺素转运体(norepinephrine transporter,NET)基因多态性的关系。方法:采用DSM-Ⅳ轴Ⅰ结构式临床访谈选取139例惊恐障碍患者(惊恐障碍组)和196例正常健康对照(对照组)。采用imLDRTM多重单核苷酸多态性(single nucleotide polymorphism,SNP)分型试剂盒对所有样本进行6个SNP位点分型,采用SPSS 16.0和PLINK比较等位基因频率及基因型分布差异。结果:(1)惊恐障碍组在NET rs5569多态性上携带G等位基因(76.3%)高于正常对照组(68.4%),携带A等位基因(23.7%)少于对照组(31.6%),差异有统计学意义(χ2=4.986,OR=0.67,95%CI=0.47~0.95,P<0.05),而多重校正后差异无统计学意义(P>0.05)。(2)加性模型显示惊恐障碍组与正常对照组在NET rs5569多态性各基因型上差异有统计学意义(OR=0.68,95%CI=0.48~0.96,P<0.05);隐性模型显示惊恐障碍组与正常对照组在DβH rs1611114多态性的基因型上差异有统计学意义(OR=0.42,95%CI=0.18~0.96,P<0.05),但多重校正后均差异无统计学意义(P>0.05)。(3)无论是等位基因还是基因型,惊恐障碍组与正常对照组在DβH(rs129882、rs1611114、rs1611115)和NET(rs2242446、rs28386840)基因多态性上均差异无统计学意义(均P>0.05)。结论:DβH和NET基因多态性与惊恐障碍可能不存在关联。

Objective To explore the association between dopamine-β-hydroxylase(DβH),norepinephrine transporter(NET)gene polymorphisms and panic disorder(PD).Methods The structured clinical interview for the diagnostic and statistical manual of mental disorders fourth edition(DSM-Ⅳ)axisⅠdisorders was administered by trained clinical psychiatrist,139 patients with PD(PD group)and 196 healthy controls(control group)were enrolled in the study.Single nucleotide polymorphism(SNP)genotyping was performed using an improved multiplex ligation detection reaction technique.SPSS 16.0 and PLINK softwares were used to compare the allele frequency and genotype distribution.Results(1)Compared with control group,PD group carried more G allele(76.3%vs 68.4%)and fewer A allele(23.7%vs 31.6%)in NET rs5569,and the difference was significant(χ2=4.986,OR=0.67,95%CI:0.47-0.95,P<0.05).However,the correlation was no longer significant after adjusting for Bonferroni’s multiple testing(P>0.05).(2)The additive model of NET rs5569 showed a association with PD(OR=0.68,95%CI:0.48-0.96,P<0.05).And the recessive model of DβH rs1611114 showed a association with PD(OR=0.42,95%CI:0.18-0.96,P<0.05).However,these correlations were no longer significant after adjusting for Bonferroni's multiple testing(P>0.05).(3)No matter allele or genotype,there were no significant differences in DβH(rs129882,rs1611114,rs1611115)and NET(rs2242446,rs28386840)gene polymorphisms between panic disorder group and control group(all P>0.05).Conclusion The present study indicates that there is no significant association of DβH and NET gene polymorphisms with PD.