5-HTR2A-1438A/G、COMTVal158Met、MAOA-LPR、5-HTTVNTR、DATVNTR与男性海洛因依赖共患反社会性人格障碍的关联研究

ASSOCIATION STUDY OF 5-HTR2A-1438A/G,COMTVAL158MET,MAOA-LPR,DATVNTR AND 5-HTTVNTR POLYMORPHISMS WITH COOCCURRENCE HEROIN DEPENDENCE AND ANTISOCIAL PERSONALITY DISORDERS IN MALES

目的:探讨5-HTR2A受体基因(5-hydroxytryptamine receptor 2 Agene,5-HTR2A)-1438A/G多态性(5-HTR2A-1438A/G,rs6311)、儿茶酚-O-甲基转移酶基因(catechol-O-methyltransferase gene,COMT)Val158Met多态性(COMTVal158Met,rs4680)、单胺氧化酶A基因(monoamine oxidase Agene,MAOA)启动子区可变数目串联重复序列(variable number of tandem repeats,VNTR)多态性(称为MAOA多型变异区段,MAOA-linked polymorphic region,MAOA-LPR))、多巴胺转运体基因(dopamine transporter gene,DAT)外显子15靠近3′端的可变数目串联重复序列多态性(DATVNTR)、5-HT转运体基因(5-hydroxytryptamine transporter gene,5-HTT)内含子2内可变数目串联重复序列多态性(5-HTTVNTR)及以上各位点之间的交互作用与男性海洛因依赖共患反社会性人格障碍有无关联。方法:采用病历对照关联分析,应用聚合酶链式反应和连接酶检测反应(polymerase chain reaction-ligase detection reaction,PCR-LDR)技术检测588例男性海洛因依赖者(其中共患反社会性人格障碍者311例,不共患反社会性人格障碍者277例)和194例健康男性5-HTR2A-1438A/G、COMTVal158Met、MAOA-LPR、DATVNTR、5-HTTVNTR多态性的基因型,对各位点的基因型频率、等位基因频率及各位点之间的交互作用进行疾病关联分析。结果:共患反社会性人格障碍的男性海洛因依赖者与健康男性间,共患与不共患反社会性人格障碍的男性海洛因依赖者间在5-HTTVNTR的基因型和等位基因频率上均有统计学差异,携带10次重复序列(10-repeats,10R)等位基因的个体共患海洛因依赖和反社会性人格障碍风险相对较大。经MDR分析,在男性海洛因依赖者中,HTTVNTR与DATVNTR的二因模型子对反社会性人格障碍的预测准确度最大,符号检验有统计学差异,校正后P值为0.067,接近显著性差异。携带5-HTTVNTR等位基因10R和/或携带DATVNTR等位基因9R的个体共患反社会性人格障碍的风险相对较大,而当个体的5-HTTVNTR基因型为纯合的12R/12R且DATVNTR基因型为纯合的10R/10R时,共患反社会性人格障碍的风险相对较小。结论:5-HTTVNTR、5-HTTVNTR与DATVNTR的交互作用与男性海洛因依赖共患反社会性人格障碍相关联。

Objective：To explore the association of the 5-HTR2A-1438A/G,COMTVal158Met,MAOA-LPR,DATVNTR and 5-HTTVNTR polymorphisms with cooccurrence heroin dependence and antisocial personality disorders in males. Methods：In case control study,we compared the polymorphic distributions of 5-HTR2A-1438A/G,COMTVal158Met,MAOA-LPR,DATVNTR and 5-HTTVNTR in 588 male heroin dependent patients（including 311 patients with antisocial disorder and 277 patients without antisocial disorder） and 194 healthy males by genotypes,alleles,and interaction between locies. Results：Between male heroin dependent patients with antisocial disorder and healthy males,and between those with cooccurrence antisocial disorder and those without cooccurrence antisocial disorder in male heroin dependent patients,the distributions of 5-HTTVNTR polymorphic genotypes and allelles showed statistical significance. Individuals carrying 10 R allele were in higher risk of cooccurrence heroin dependence and antisocial personality disorders. By MDR analysis,the interaction between HTTVNTR and DATVNTR was in marginal significance in prediction to risk of antisocial disorder in male heroin dependent patients. In male heroin dependent patients,individuals carrying 5-HTTVNTR 10 R allele or/and DATVNTR 9 R were in higher risks of cooccurrence antisocial personality disorders,while individuals with 5-HTTVNTR 12 R/12 R and DATVNTR 10 R/10 R genotypes together might be in lower risks of antisocial personality disorder. Conclusion：5-HTTVNTR,and the interaction between 5-HTTVNTR and DATVNTR were in association with cooccurrence heroin dependence and antisocial personality disorders in males.