多巴胺D2受体基因多态性与利培酮致高泌乳素血症的相关性  

Association between dopamine D2 receptor gene polymorphism and risperidone induced hyperprolactinemia

作　　者：曹钰羚 陈永刚 张钦宇 张宏 周晓亮[3] 郭岳翰[3] 邹吉利 孟军华[2] 王雄[2] 吴金虎[2] 安靖[2] CAO Yu-ling;CHEN Yong-gang;ZHANG Qin-yu;ZHANG Hong;ZHOU Xiao-liang;GUO Yuehan;ZOU Ji-li;MENG Jun-hua;WANG Xiong;WU Jin-hu;AN Jing(School of Medicine,Wuhan University of Science&Technology,Hubei Wuhan430065,China;Affiliated Tongren Hospital,Wuhan University,Third Municipal Hospital,Hubei Wuhan 430060,China;Wuhan Mental Health Center,Municipal Psychological Hospital,Hubei Wuhan 420104,China)

机构地区：[1]武汉科技大学医学院,湖北武汉430065 [2]武汉大学附属同仁医院,武汉市第三医院,湖北武汉430060 [3]武汉市精神卫生中心,武汉市心理医院,湖北武汉420104

出　　处：《中国医院药学杂志》2021年第24期2547-2551,共5页Chinese Journal of Hospital Pharmacy

基　　金：武汉市卫生健康委员会科研项目(编号:WZ21Q03);武汉市卫生健康委员会重大项目(编号:WZ21M03);武汉市应用基础前沿项目(编号:2020020601012301)。

摘　　要：目的:探讨多巴胺D2受体基因多态性与利培酮致高泌乳素血症的相关性。方法:纳入115例接受单一利培酮治疗的精神分裂症患者为研究对象,于治疗前后测定血清泌乳素水平,根据泌乳素水平>25 ng·mL^(-1)和≤25 ng·mL^(-1),分为高泌乳素血症(hyperprolactinemia,HPRL)组和泌乳素水平正常(normal prolactinemia,NPRL)组。并采用PCR重测序法检测受试者DRD2受体rs1799732、rs1800497、rs1799978、rs6275、rs6279以及rs6280基因多态性,多因素Logistic回归分析各基因型和利培酮致HPRL的相关性。结果:HPRL组与NPRL组rs1799732基因型等位基因频率组间差异有统计学意义(χ^(2)=12.705,P=0.0005);HPRL组与NPRL组rs6279基因型等位基因频率组间差异有统计学意义(χ^(2)=11.267,P=0.003),而rs1799978、rs1800497、rs6275、rs6280位点基因型和等位基因频率分布差异均无统计学意义(P>0.05)。rs1799732位点Ins/Del和Del/Del型患者服用利培酮后致HPRL的可能性分别是野生型Ins/Ins的4.357倍(1.135~12.178)和1.418倍(0.312~5.337);而rs6279位点CG和GG型患者服用利培酮后致HPRL的可能性分别是野生型CC的9.189倍(2.756~18.534)和3.265倍(0.786~10.532)。结论:DRD2-rs1799732*Del和rs6279*C是利培酮所致HPRL的易感基因。OBJECTIVE To explore the association between dopamine D2 receptor gene polymorphism and risperidone induced hyperprolactinemia(HPRL).METHODS A total of 115 schizophrenics treated with risperidone alone were included.Serum levels of prolactin were measured before and after treatment.According to a cutoff prolactin level of>25 or≤25 ng·mL^(-1),they were divided into two groups of hyperprolactinemia(HPRL)and normal prolactin level(NPRL).The polymorphisms of DRD2 receptor genes rs1799732,rs1800497,rs1799978,rs6275,rs6279 and rs6280 were detected by polymerase chain reaction(PCR)sequencing.And the correlation between genotypes and HPRL was analyzed by multivariate Logistic regression.RESULTS Significant difference existed in rs1799732 genotypic allele frequency between HPRL and NPRL groups(χ^(2)=12.705,P=0.0005);significant inter-group difference in rs6279 genotypic allele frequency(χ^(2)=11.267,P=0.003).However,there was no significant difference in genotype or allele frequency distribution among rs1799978,rs1800497,rs6275 and rs6280(P>0.05).The probability of HPRL caused by risperidone in patients with INS/del and del/del at rs1799732locus was 4.357 folds(1.135-12.178)and 1.418 folds(0.312-5.337)higher than that of wild-type INS/INS respectively;The probability of HPRL caused by risperidone in CG/GG patients at rs6279 locus was 9.189 folds(2.756-18.534)and 3.265 folds(0.786-10.532)higher than that of wild-type CC.CONCLUSION DRD2-rs1799732*Del and rs6279*C are the susceptible genes of risperidone induced HPRL.

关 键 词：利培酮 高泌乳素血症 多巴胺D2受体 基因多态性 

分 类 号：R971.4[医药卫生—药品]