HTR 2A基因6个单核苷酸多态性与海洛因依赖的关联性研究  

Association between HTR 2A Gene Polymorphism and Heroin Dependence

作　　者：贾维 栾鹏飞 马占兵[1,2] 彭亮[1] 钟慧军[1,2] 党洁[1,2] 朱永生 JIA Wei;LUAN Pengfei;MA Zhanbing;PENG Liang;ZHONG Huijun;DANG Jie;ZHU Yongsheng(School of Basic Medicine,Ningxia Medical University,Yinchuan750004,China;Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education,Ningxia Medical University,Key Laboratory of Reproduction and Genetics of Ningxia Hui Autonomous Region,Yinchuan750004,China;Department of Forensic Physical Evidence,College of Forensic Science,Xi’an Jiaotong University,Xi’an710061,China)

机构地区：[1]宁夏医科大学基础医学院,银川750004 [2]宁夏医科大学生育力保持教育部重点实验室,宁夏回族自治区生殖与遗传重点实验室,银川750004 [3]西安交通大学医学部法医学院法医物证系,西安710061

出　　处：《宁夏医科大学学报》2019年第9期865-870,共6页Journal of Ningxia Medical University

基　　金：国家自然科学基金(31460288);宁夏医科大学特殊人才启动项目(XT2017001)

摘　　要：目的探讨5-羟色胺2A受体(5-hydroxytryptamine/serotonin 2A receptor,HTR2A)基因6个单核苷酸多态性(single nucleotide polymorphism,SNP)与海洛因依赖之间的关系。方法严格按照诊断标准,选取无亲缘关系的海洛因依赖患者396例和健康对照401例,提取外周血DNA,采用SNaPshot SNP分型技术对HTR2A基因的6个SNPs(rs3125,rs6311,rs6313,rs7324017,rs732821,rs731245)进行基因分型,比较海洛因依赖组与对照组各位点等位基因型、基因型频率的差异。结果HTR2A基因rs3125、rs6311、rs6313、rs7324017和rs732821位点的等位基因频率在海洛因依赖组和对照组之间差异均有统计学意义(P均<0.05)。HTR2A rs3125 C等位基因(P<0.001,OR=1.81,95%CI:1.39~2.35),rs7324017 C等位基因(P<0.001,OR=1.79,95%CI:1.38~2.33)及rs732821 C等位基因(P=0.029,OR=1.33,95%CI:1.03~1.73)会增加海洛因依赖的发病风险,而rs6311 T等位基因(P=0.037,OR=0.81,95%CI:0.67~0.99),rs6313 A等位基因(P=0.022,OR=0.79,95%CI:0.65~0.97)则是海洛因依赖的保护性因素。同时,通过连锁不平衡分析,处于block1的两位点(rs7324017-rs3125)构成的G-T单倍型在两组间差异有统计学意义(P<0.001,OR=0.61,95%CI:0.47~0.80)。结论HTR2A基因的6个SNPs位点中有5个位点与中国人群海洛因依赖相关,提示HTR2A可能是海洛因依赖的易感基因。Objective To discuss the association between 6 single nucleotide polymorphism(SNP)sites and heroin dependence of serotonin 2A receptor(HTR2A)gene.Methods According to the diagnostic criteria,genomic DNA was isolated from 396 unrelated heroin dependent individuals and 401 healthy unrelated individuals.Polymorphism of rs3125,rs6311,rs6313,rs7324017,rs732821 and rs731245 were genotyped by SNaPshot SNP technique to compare the allele and genotype frequencies between the case-control group.Results There were significant differences in allele frequencies of rs3125,rs6311,rs6313,rs7324017 and rs732821 between the case and control group(P all<0.05).The C allele of rs3125(P<0.001,OR=1.81,95%CI:1.39-2.35),the C allele of rs7324017(P<0.001,OR=1.79,95%CI:1.38-2.33)and rs732821 C allele(P=0.029,OR=1.33,95%CI:1.03-1.73)were risk factors for heroin dependence,otherwise,the T allele of rs6311(P=0.037,OR=0.81,95%CI:0.67-0.99)and rs6313 A allele(P=0.022,OR=0.79,95%CI:0.65-0.97)were protective factors for heroin dependence.Moreover,we found the frequency of G-T(rs7324017-rs3125)haplotype in block1(P<0.001,OR=0.61,95%CI:0.47~0.80)showed significant difference between heroin dependence and controls.Conclusion Five of the six loci that we studied in HTR2A were associated with heroin addiction,which means HTR2A may be the susceptibility gene to heroin dependence.

关 键 词：5-羟色胺2A受体基因 5-羟色胺2A受体 海洛因依赖 单核苷酸多态性 

分 类 号：R394.6[医药卫生—医学遗传学] R395.6[医药卫生—基础医学]