多巴胺受体基因多态性与海洛因依赖的关联性研究

Association between the Polymorphisms dopamine receptor gene and heroin dependence

目的探讨多巴胺D1受体基因-48A/G、D2受体基因Taq1A及-141 ins/del、D3受体基因Ser 9Gly、D4受体基因-521C/T 5个多态性位点与海洛因依赖的相关性。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304例(海洛因依赖组)及健康体检者(正常对照组)320例提取基因组DNA,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测5个多态性位点的基因型,采用SPSS 11.5软件分析各位点基因型、等位基因频率及组间差异。结果多巴胺D2受体基因Taq1A位点的基因型及等位基因频率分布在海洛因依赖组与正常对照组间差异有统计学意义(P<0.05),海洛因依赖组Taq1A位点的等位基因A1频率显著高于正常对照组(χ2=5.591,P=0.018,OR=1.314,95%CI=1.048～1.647);多巴胺D4受体基因-521C/T位点的基因型及等位基因频率分布在海洛因依赖组与正常对照组间差异有统计学意义(P<0.05),海洛因依赖组等位基因T频率显著高于正常对照组(χ2=9.663,P=0.002,OR=1.224,95%CI=0.970～1.545)。结论多巴胺D2受体基因Taq1A和多巴胺D4受体基因-521C/T位点多态性可能与海洛因依赖有关,携带有Taq1A多态性位点A1等位基因与-521C/T多态性位点T等位基因的个体可能更容易对海洛因产生依赖。

【Objective】 To study a possible association between the dopamine D1 receptor Gene-48A/G,dopamine D2 receptor Gene Taq1A and-141 ins/del,dopamine D3 receptor Gene Ser9Gly,and dopamine D4 receptor Gene-521C/T polymorphisms and heroin dependence.【Methods】 Genomic DNA was isolated from the venous blood leukocytes of 304 unrelated patients with heroin dependence and 320 healthy unrelated individuals（Control group）.The 5 SNPs were genotyped by PCR-restriction fragment length polymorphisms（PCR-RFLP）.Genotype,and allele frequencies were analyzed by SPSS 11.5 software.【Results】 There were significant differences in both allele and genotype frequencies of Taq1A between the study and control group（P 0.05）.The allele A1 of Taq1A was significantly higher than controls（χ2=5.591,P =0.018,OR=1.314,95%CI=1.048～1.647）.There were significant differences in both allele and genotype frequencies of-521C/G between the Study and Control group（P 0.05）.The allele T of-521C/T was significantly higher than controls（χ2=9.663,P =0.002,OR=1.224,95%CI=0.970～1.545）.【Conclusions】 There is an association between Taq1A,-521C/T polymorphism and heroin dependence.The individuals with A1 allele of Taq1A and T allele of-521C/T are susceptible to heroin dependence.