SLC6A4基因多态性与海洛因依赖的关联性研究

目的:探讨5-羟色胺转运体基因(solute carrier family 6 member 4,SLC6A4)基因4个单核苷酸多态性(single nucleotide polymorphism,SNP)位点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个体397例(病例组)及健康对照个体402例(对照组)提取基因组DNA,采用SNaPshot SNP分型技术对SLC6A4基因4个SNP位点(rs1042173,rs3813034,rs6354,rs7224199)进行基因分型,比较病例-对照组间各位点等位基因、基因型频率的差异。结果:病例组和对照组SLC6A4基因rs1042173和rs3813034位点的基因型和等位基因频率比较存在显著性差异(P0.05),rs1042173的C等位基因(P=0.031,OR=1.317,95%CI=1.026-1.691)及rs3813034的C等位基因(P=0.013,OR=1.375,95%CI=1.069-1.768)是海洛因依赖的危险因素。病例组TCC单倍型(rs7224199、rs3813034和rs1042173)的比例较对照组显著增高(P0.05)。结论:SLC6A4基因rs1042173和rs3813034多态性可能与海洛因成瘾有关,携带有rs1042173的C等位基因和rs3813034的C等位基因的个体及携带TCC单倍型的个体可能更容易对海洛因产生依赖。

Association between SLC6A4 Gene Polymorphism and Heroin Dependence

ABSTRACT Objective: To discuss the association between 4 single nucleotide polymorphism (SNP) sites and heroin dependence of solute carrier family 6 member 4 (SLC6A4) gene. Methods: According to the diagnostic criteria, genomic DNA was isolated from 397 unrelated heroin dependent individuals (case group) and 402 healthy unrelated individuals (control group). Polymorphism of rs1042173, rs3813034, rs6354, rs7224199 were genotyped by SNaPshot SNP technique to compare the allele and genotype frequencies between the case-control group. Results: There were significant differences in both allele and genotype frequencies of rs1042173 and rs3813034 be- tween the case and control group (P<0.05). The C allele of rs1042173 (P=0.031, OR=1.317, 95% CI =1.026-1.691) and the C allele of rs3813034 (P=0.013, OR=1.375, 95% CI =1.069-1.768) were risk factors for heroin dependence. Moreover, we found the frequency of TCC (rs7224199, rs3813034, rs1042173) haplotype was significantly higher in heroin dependence than those in the controls. Conclusion: SLC6A4 gene rs1042173 and rs3813034 polymorphisms may be related to heroin addiction. Individuals carrying the C allele of rs1042173 and the C allele of rs3813034 and the carrier with haplotype TCC may be susceptible to heroin dependence.