强迫症药物疗效与六个功能基因的分子遗传药理学研究

目的　探讨与5-羟色胺系统和多巴胺系统有关的6个基因(5-羟色胺2A受体基因、5-羟色胺转运体基因、多巴胺D2受体基因、多巴胺D4受体基因、儿茶酚胺氧位甲基转移酶基因、单胺氧化酶A基因)与强迫症药物疗效之间是否存在关联。方法　收集了113个强迫症核心家系,对强迫症患者给予5-羟色胺回吸收抑制剂治疗,采用Yale-Brown强迫量表在治疗8周前后进行评定,按Yale-Brown强迫量表评分分为有效组和无效组。采用限制性片段长度多态性和可变数串联重复序列多态性技术对有效组和无效组的强迫症家系在6个基因的7个位点上进行传递不平衡检测。结果　未发现6个基因与不同药效的强迫症家系之间存在关联,但发现有效组和无效组在5-羟色胺2A受体基因-1438G/A位点基因型频率存在差异,无效组有更多的纯合子(χ2=4.69,P=0.03)。结论　5-羟色胺2A受体基因可能和强迫症药物治疗效果有关。

Molecular pharmacogenetic studies of drug responses to obsessive-compulsive disorder and six functional genes

OBJECTIVE: To investigate the associations between the drug responses to obsessive -pulsive disorder (OCD) and six functional genes related with serotonin and dopamine. METHODS: One hundred and thirteen OCD nuclear families were collected. The OCD patients were treated with serotonin reuptake inhibitors (SRIs) for 8 weeks and the drug responses were assessed using the Yale-Brown obsessive-compulsive scale (Y-BOCS). The patients were divided into drug responders group and non-responders group according to the reducing rate of Y-BOCS score. The genotypes of six genes were determined with the Amp-FLP and Amp-RFLP techniques and analyzed by transmission disequilibrium test (TDT). The six genes are serotonin 2A receptor (5-HT2A), serotonin transporter (5-HTT), dopamine D2 receptor ( DRD2), dopamine D4 receptor (DRD4), catechol-O- methyltransferase (COMT) and monoamine oxidase A (MAOA). RESULTS: No association was found between the six genes and different drug responses groups. However, there was significant difference between the drug responders and non-responders in homozygosity at the 5-HT2A -1438G/A locus (chi(2)=4.69, P=0.03). CONCLUSION: The results suggested that the 5-HT2A may play some roles in the effects of drug treatment on OCD.