多巴胺受体D2基因启动子区CpG岛DNA甲基化与持续性姿势-知觉性头晕的关系分析

Association between DNA methylation in the CpG island of dopamine D2 receptor gene promoter region and persistent postural-perceptual dizziness

目的探讨多巴胺受体D2(DRD2)基因启动子区CpG岛DNA甲基化水平与持续性姿势-知觉性头晕(PPPD)发病的关系。方法对自2017年1月至6月在烟台市烟台山医院神经内科确诊的43例PPPD患者(试验组)于收治时采集血样,对同期收治的未予选择性5-羟色胺再摄取抑制剂(SSRI)类或5-羟色胺和去甲肾上腺素再摄取抑制剂(SNRI)类药物治疗的、且随访3个月以上头晕症状未再发而排除PPPD诊断的45例急性前庭外周性眩晕患者(对照组)于随访时采集血样,应用重亚硫酸盐测序法进行基因启动子区CpG岛甲基化水平的检测并比较2组间的差异。结果试验组DRD2基因启动子区CpG岛的甲基化阳性率(58.1%)明显高于对照组(15.6%),CpG岛位点甲基化率(0.15±0.18)明显高于对照组(0.04±0.10),差异均有统计学意义(P<0.05)。结论PPPD发病可能与患者基因启动子区CpG岛DNA甲基化水平增高有关。

Objective To analyze the relation between DNA methylation in the CpG island of dopamine D2 receptor(DRD2)gene promoter region and persistent postural-perceptual dizziness(PPPD),and explore the molecular mechanism of PPPD.Methods The disease group consisted of 43 patients diagnosed as having PPPD in our hospital from January 2017 to June 2017,and blood samples were taken at admission.The control group included 45 with acute vestibular peripheral vertigo whose dizziness symptoms did not recrudesce after follow-up for more than 3 months and PPPD diagnosis was excluded in our hospital at the same period;these patients did not take selective serotonin reuptake inhibitors(SSRIs)or serotonin norepinephrine reuptake inhibitors(SNRIs);blood samples in the patients were collected during follow-up.DNA methylation in the CpG island of DRD2 promoter region was detected by disulfite sequencing and the differences between the two groups were compared.Results The positive rate of DNA methylation in the CpG island of DRD2 promoter region in the disease group was 58.1%,which was significantly higher than that in the control group(15.6%,P<0.05);and the methylation rate of CpG island loci in the disease group(0.15±0.18)was significantly higher than that in the control group(0.04±0.10,P<0.05).Conclusion The DNA methylation in the CpG island of DRD2 promoter region is associated with onset of PPPD.