5-羟色胺受体基因多态性位点与海洛因依赖的关联性研究

Association between the Polymorphisms Serotonin Receptor Gene and Heroin Dependence

目的：5-HT（5-hydroxytryptamine,5-HT）参与了多种中枢神经活动的生理过程,其功能异常可以影响很多行为障碍,已有研究显示,5-HT水平与多种精神疾病密切相关。5-HT受体及其转运体基因在海洛因依赖发生发展中起到了重要的作用,是海洛因依赖的主要候选基因。探讨5羟色胺2A受体（Serotonin 2A receptor,HTR2A）基因启动子区-1438A/G（rs6311）、外显子区102T/C（rs6313）与5羟色胺1B受体（Serotonin 1B receptor,HTR1B）基因外显子区861G/C（rs6296）3个单核苷酸多态性和海洛因依赖的关联性分析。方法：严格按照诊断标准,选取无亲缘关系的海洛因依赖个体616例及健康个体600例提取基因组DNA,采用PCR-RFLP方法检测rs6311、rs6313和rs6296 3个SNPs位点的基因型频率,采用SPSS16.0软件分析各位点等位基因、基因型频率在病例-对照组间差异。结果：HTR2A基因rs6311和HTR1B基因rs6296位点的等位基因及基因型频率分布在2组间存在统计学差异（P〈0.05）,病例组rs6311位点的等位基因A频率显著高于对照组（X2=5.436,P=0.020,OR=1.208,CI=1.031~1.417）,rs6296位点的等位基因C频率显著高于对照组（X2=12.116,P=0.000,OR=1.329,CI=1.132~1.560）。连锁不平衡检验结果显示,HTR2A基因rs6311、rs6313位点处于不连锁状态,D＇〈0.5。结论：HTR2A基因rs6311和HTR1B基因rs6296多态性可能与海洛因成瘾有关,携带有rs6311 A等位基因与rs6296 C等位基因的人可能更容易对海洛因产生依赖。我们的研究为海洛因依赖易感人群筛选及药物靶向治疗提供了理论依据。

Objective： Serotonin 5-HT（5-hydroxytryptamine, 5-HT has been implicated in a variety of behavioral and physiological processes mediated by the central nervous system, and its dysfunction can affect many behavioral disorders, and closely related a variety of psychiatric disorders. Candidate gene-based association showed that serotonin 5-HT receptor family have important role in heroin dependence. To study a possible association between the-1438A/G（rs6311）, 102T/C（rs6313） of the Serotonin 2A receptor（HTR2A） gene, 861G/C（rs6296） of Serotonin 1B receptor（HTR1B） gene SNPs polymorphisms and heroin dependence. Methods：Genomic DNA was isolated from the venous blood leukocytes of 616 unrelated patients with heroin dependence and 600 healthy unrelated individuals（Control group）. Polymorphism of rs6311, rs6313 and rs6296, were genotyped by PCR-restriction fragment length polymorphisms（PCR-RFLP）. Genotype, and allele frequencies were analysed by HaploView4.0 and SPSS11.5 software. Results： There were significant differences in both allele and genotype frequencies of rs6311 and rs6296 between the Study and Control group. The allele A of rs6311 was significantly higher than controls（X2=5.436, P=0.020, OR=1.208, 95%CI=1.031~1.417）, the allele C of rs6296was significantly higher than controls（X2=12.116, P=0.000, OR=1.329, 95%CI=1.132~1.560）.Linkage disequilibrium was not observed between rs6311 and rs6313. Conclusion： There is an association between rs6311, rs6296 polymorphism and heroin dependence. The individuals with A allele of rs6311 and C allele of rs6296 are susceptible to heroin dependence. Our study provides a theoretical basis on susceptible populations and targeted therapy.