DCC、FAT3、DLG2、KTN1基因多态性与海洛因依赖的相关性研究  

Association between polymorphism of DCC,FAT3,DLG2,KTN1 and heroin dependence

作　　者：贾维 栾鹏飞 马占兵[1,2] 彭亮 钟慧军[1,2] 朱永生[3] 党洁 JIA Wei;LUAN Pengfei;MA Zhanbing;PENG Liang;ZHONG Huijun;ZHU Yongsheng;DANG Jie(College of Basic Medicine,Ningxia Medical University,Yinchuan,Ningxia 750004,China;Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education,Yinchuan,Ningxia 750004,China;Forensic Material Evidence,Institute of Forensic Medicine,Xi′an Jiaotong University Health Science Center,Xi′an,Shaanxi 710061,China)

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

出　　处：《国际检验医学杂志》2021年第8期897-901,共5页International Journal of Laboratory Medicine

基　　金：国家自然科学基金项目(81960306);宁夏高等学校科学研究项目(NXCX2018120)。

摘　　要：目的探讨结肠癌缺失基因(DCC)、非典型钙黏蛋白3基因(FAT3)、成虫大盘基因同源物2(DLG2)和驱动结合蛋白1基因(KTN1)4个单核苷酸多态性(SNP)位点与海洛因依赖之间的关系。方法采用SNaPshot SNP分型技术对396例海洛因依赖患者(海洛因依赖组)及401例健康对照者(健康对照组)DCC(rs2270954)、FAT3(rs1318862)、DLG2(rs683250)和KTN1(rs945270)位点进行基因分型,比较两组间各位点等位基因、基因型频率的差异,同时利用多维因子降维法(MDR)和二元Logistic回归分析4个位点基因间交互作用。结果DCC(rs2270954)位点及KTN1(rs945270)位点的等位基因和基因型频率在健康对照组和海洛因依赖组间差异有统计学意义(P<0.05),携带DCC(rs2270954)A等位基因及KTN1(rs945270)C等位基因的个体发生海洛因依赖的可能性更高。此外,DCC(rs2270954)与KTN1(rs945270)位点间存在显著二维基因交互作用,提示二者可能通过上位效应影响DCC和KTN1的表达水平,进而异常调节中脑边缘奖赏系统,产生海洛因依赖。结论DCC(rs2270954)及KTN1(rs945270)位点基因多态性可能与海洛因成瘾有关,且二者可能通过交互作用影响大脑奖赏效应的调节。Objective To investigate the association between 4 single nucleotide polymorphisms(SNPs)sites from Deleted in Colorectal Cancer(DCC),FAT atypical cadherin3(FAT3),Discs large homolog 2(DLG2)and Kinectin 1(KTN1)genes and heroin dependence.Methods SNaPshot SNP technique was used to compare the allele and genotype frequencies of DCC(rs2270954),FAT3(rs1318862),DLG2(rs683250)and KTN1(rs945270)between 396 heroin dependent individuals and 401 healthy controls.Furthermore,multifactor dimensionality reduction(MDR)and binary Logistic regression were used to analyze the gene interaction.Results The allele and genotype frequencies of DCC(rs2270954)and KTN1(rs945270)showed the significant difference between healthy controls and heroin dependence group(P<0.05).Individuals with DCC(rs2270954)A allele and KTN1(rs945270)C allele may be more susceptible to heroin dependence.In addition,there was a significant two-dimensional interaction between DCC(rs2270954)and KTN1(rs945270),suggesting that they may affect the expression of DCC and KTN1 genes through epistatic effects,and then abnormally regulate the brain reward system,resulting in heroin dependence.Conclusion DCC(rs2270954)and KTN1(rs945270)may be associated with heroin dependence,and they may affect the regulation of brain rewarding effects through interaction.

关 键 词：海洛因依赖 奖赏效应 基因交互 基因多态性 

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