HTR1A、HTR1B基因多态性与海洛因依赖的关联性研究

Association between HTR1A,HTR1B Gene Polymorphism and Heroin

目的 探讨5-羟色胺1A及1B受体(HTR1A、HTR1B)基因共9个单核苷酸多态性(SNPs)与海洛因依赖的关联性。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392例和401例健康对照为研究对象,提取外周血DNA,采用SNaPshot SNP基因分型技术对HTR1A和HTR1B基因共9个SNPs(rs878567、rs6449693、rs6294、rs1228814、rs1778258、rs4140535、rs6296、rs6297、rs6298)进行基因分型,采用SNPStats在线统计软件和广义多因子降维法(GMDR)分别进行海洛因依赖组与对照组各位点等位基因型和基因型频率分析及基因间交互分析。结果 rs878567 A等位基因(P=0.045,OR=0.77,95%CI:0.59~0.99)、rs6449693 G等位基因(P=0.040,OR=0.77,95%CI:0.59~0.99)、rs6296 C等位基因(P=0.022,OR=0.79,95%CI:0.65~0.97)及rs6298G等位基因(P=0.012,OR=0.78,95%CI:0.64~0.95)均是海洛因依赖的保护性因素;而携带rs6294 T等位基因的个体发生海洛因依赖的风险增高(P=0.028,OR=1.55,95%CI:1.04~2.29)。HTR1B基因TCGGCA单倍型(rs6297-rs6296-rs6298-rs1228814-rs1778258-rs4140535)在两组间差异具有统计学意义(P=0.014,OR=0.598,95%CI:0.395~0.905),是海洛因依赖的保护性因素。此外,rs878567-rs4140535-rs6296三阶交互模型是海洛因依赖的危险因素(P=0.006,OR=3.087,95%CI:0.952~10.016)。结论 HTR1A和HTR1B基因共5个单核苷酸多态性位点与人群海洛因依赖的易感性存在一定关联性,且二者可能通过交互作用影响大脑奖赏效应的调节,进而参与海洛因依赖的形成。

Objective To investigate the association between 9 single nucleotide polymorphisms(SNPs)of 5-hydroxytryptamihe 1A and 1B receptor(HTR1A、HTR1B)genes and heroin dependence.Methods According to the diagnostic criteria,392 unrelated heroin dependent patients and 401 healthy controls were selected as the study objects,and peripheral blood DNA was extracted.Nine SNPs(rs878567,rs6449693,rs6294,rs1228814,rs1778258,rs4140535,rs6296,rs6297,rs6298)of HTR1A and HTR1B genes were genotyped by SNaPshot SNP typing technique.SNPStats online statistical software and generalized multifactor dimensionality reduction(GMDR)were used to analyze allele,genotype frequency and gene-gene interaction between heroin dependence group and control group respectively.Results rs878567 A allele(P=0.045,OR=0.77,95%CI:0.59-0.99),rs6449693 G allele(P=0.040,OR=0.77,95%CI:0.59-0.99),rs6296 C allele(P=0.022,OR=0.79,95%CI:0.65-0.97),rs6298 G allele(P=0.012,OR=0.78,95%CI:0.64-0.95)were protective factors for heroin dependence.Individuals with rs6294 T allele(P=0.028,OR=1.55,95%CI:1.04-2.29)had a significantly higher risk of heroin dependence.The HTR1B gene TCGGCA haplotype(rs6297-rs6296-rs6298-rs1228814-rs1778258-rs4140535)was significantly different between the two groups(P=0.014,OR=0.598,95%CI:0.395-0.905),might be a protective factor for heroin dependence.In addition,the third-order interaction model rs878567-rs4140535-rs6296 was a risk factor for heroin dependence(P=0.006,OR=3.087,95%CI:0.952-10.016).Conclusion A total of 5 SNPs of HTR1A and HTR1B genes were associated with the susceptibility to heroin dependence in population,and they may affect the regulation of brain rewarding effects through interaction,and then participate in the formation of heroin dependence.