多巴胺受体基因多态性与利培酮治疗效果的关系：系统评价和荟萃分析。
Association between dopamine receptor gene polymorphisms and effects of risperidone treatment: A systematic review and meta-analysis.
机构信息
Department of Pharmacy, Peking University First Hospital, Beijing, China.
出版信息
Basic Clin Pharmacol Toxicol. 2019 Jan;124(1):94-104. doi: 10.1111/bcpt.13111. Epub 2018 Sep 11.
BACKGROUND
The effect of risperidone treatment in patients with schizophrenia varies according to the dopamine receptor genes. This study aimed to evaluate the relationship between genes of the dopamine receptors (D1, D2, and D3) and the effect of risperidone treatment.
METHODS
Three electronic databases (PubMed, Embase, and Cochrane Library) were searched for relevant cohort or case-control studies published before 9 May 2018. A systematic review and meta-analysis was performed for qualitative and quantitative assessment of the relationship between the dopamine receptors D1, D2, and D3 (DRD1, 2, and 3) and the effect of risperidone treatment. The summary odds ratio (OR) and weighted mean difference (WMD) in a random-effects model were used to measure these relationships.
RESULTS
Twelve studies involving 24 SNPs were included. DRD2 (Ser311Cys, rs1801028 Ser/Ser) significantly lowered the improvement rate (determined by the PANSS score) unlike Ser/Cys (WMD: -11.58, 95% CI: -17.35 to -5.18). For Asian patients, A241G (rs1799978) AA carriers showed greater improvement after risperidone therapy (P < 0.05). The polymorphisms of 141C Ins/Del (rs1799732), T939C (rs6275), rs6277, and TaqID (rs1800498) may also influence the treatment effect. TaqIA (rs1800497) and TaqIB (rs17294542) were not associated with the rate of response to risperidone. DRD3 was not associated with an improvement in the PANSS total score; however, Ser9Gly might be related to a change in negative symptoms. No significant effect of DRD1 (rs5326, rs4867798, rs4532, and rs11749676) was found.
CONCLUSIONS
Our result supported the hypothesis that DRD2 affected risperidone treatment. DRD1 had no significant effect on the response to risperidone, whereas DRD3 might be associated with an improvement in negative symptoms. Larger observational studies are warranted to verify these findings and identify other genetic factors involved.
背景
利培酮治疗精神分裂症患者的效果因多巴胺受体基因而异。本研究旨在评估多巴胺受体（D1、D2 和 D3）基因与利培酮治疗效果之间的关系。
方法
检索了三个电子数据库（PubMed、Embase 和 Cochrane Library），以查找截至 2018 年 5 月 9 日发表的相关队列或病例对照研究。对多巴胺受体 D1、D2 和 D3（DRD1、2 和 3）与利培酮治疗效果之间关系的定性和定量评估进行了系统评价和荟萃分析。使用随机效应模型中的汇总比值比（OR）和加权均数差（WMD）来衡量这些关系。
结果
纳入了 12 项涉及 24 个 SNP 的研究。DRD2（Ser311Cys，rs1801028 Ser/Ser）与改善率（由 PANSS 评分确定）降低显著相关，而 Ser/Cys 则无此相关性（WMD：-11.58，95%CI：-17.35 至-5.18）。对于亚洲患者，A241G（rs1799978）AA 携带者在利培酮治疗后显示出更大的改善（P<0.05）。141C Ins/Del（rs1799732）、T939C（rs6275）、rs6277 和 TaqID（rs1800498）的多态性也可能影响治疗效果。TaqIA（rs1800497）和 TaqIB（rs17294542）与利培酮的反应率无关。DRD3 与 PANSS 总分的改善无关；然而，Ser9Gly 可能与阴性症状的变化有关。未发现 DRD1（rs5326、rs4867798、rs4532 和 rs11749676）对利培酮反应有显著影响。
结论
我们的结果支持多巴胺受体 2 影响利培酮治疗的假设。DRD1 对利培酮的反应无显著影响，而 DRD3 可能与阴性症状的改善有关。需要更大的观察性研究来验证这些发现并确定其他涉及的遗传因素。
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