The Evidence for the Contribution of the Autism Susceptibility Candidate 2 (AUTS2) Gene in Heroin Dependence Susceptibility
The Evidence for the Contribution of the Autism Susceptibility Candidate 2 (AUTS2) Gene in Heroin Dependence Susceptibility
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自闭症易感性候选 2 (AUTS2) 基因对海洛因依赖易感性影响的证据
DOI：
10.1007/s12031-014-0421-5
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发表时间：
2014-12-01
影响因子：
3.1
通讯作者：
Lu, Xiao-Yun
中科院分区：
文献类型：
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作者：
Dang, Wei;Zhang, Qian;Lu, Xiao-Yun
据报道，孤独症易感性候选者2（AUTS 2）的单核苷酸多态性（SNP）rs6943555与欧洲人的饮酒量显著相关。在这项研究中，我们确定了在AUTS 2的SNP有助于遗传易感性海洛因依赖。海洛因依赖与21个SNPs的潜在关联（rs2270162，rs2851510，rs513150，rs595681，rs210606，rs10237984，rs13228123，rs10235781，rs6969375，rs6943555，rs10251416，rs17141963，rs12669427，rs723340、rs2293507、rs2293508、rs6960426、rs9886351、rs2293501、rs10277450、rs1918425）。参与者包括426名海洛因依赖患者和416名健康对照。分析单SNP关联、单倍型关联和临床表型关联。与对照组相比，海洛因依赖组rs6943555基因AA纯合子的频率显著增高（P= 0.0019）。海洛因依赖组A等位基因频率显著高于对照组（P= 0.0003，OR = 1.429，95%可信区间（CI）= 1.175-1.738）。在5个区组中观察到强连锁不平衡（LD）（D' > 0.9）.在区组2中，海洛因依赖者A-A单倍型显著增多（经Bonferroni校正后P= 0.006），T-A单倍型显著减少（P= 0.040）。rs6943555基因型与临床表型的相关性研究显示，AA基因型患者的海洛因自我注射量低于AT + TT基因型患者（P< 0.01）。我们的研究结果证实，除了海洛因的消费，SNP rs6943555的AUTS 2也可能在海洛因依赖的病因学中发挥重要作用。
The single-nucleotide polymorphisms (SNP) rs6943555 in autism susceptibility candidate 2 (AUTS2) has been reported to be significantly associated with alcohol consumption in Europeans. In this study, we identified the SNP in AUTS2 contributing to the genetic susceptibility to heroin dependence. The potential association between heroin dependence and 21 SNPs (rs2270162, rs2851510, rs513150, rs595681, rs210606, rs10237984, rs13228123, rs10235781, rs6969375, rs6943555, rs10251416, rs17141963, rs12669427, rs723340, rs2293507, rs2293508, rs6960426, rs9886351, rs2293501, rs10277450, rs1918425) of AUTS2 was examined in a Chinese Han population using the MassARRAY system. The participants included 426 patients with heroin dependence and 416 healthy controls. Single SNP association, haplotype association, and clinical phenotype association were analyzed. Single SNP association revealed that AA homozygotes of rs6943555 were significantly over-represented in the patients with heroin dependence compared with the control subjects (P= 0.0019). The patients with heroin dependence had a significantly higher frequency of the A allele (P= 0.0003, odd ratio (OR) = 1.429, 95 % confidence interval (CI) = 1.175–1.738). Strong linkage disequilibrium (LD) was observed in five blocks (D’ > 0.9). In block 2, significantly more A-A haplotypes (P= 0.006 after Bonferroni corrections) and significantly fewer T-A haplotypes (P= 0.040) were found in the patients with heroin dependence. The genotype and clinical phenotype correlation study of the rs6943555 carriers showed that the amount of heroin self-injection was lower in the patients with the AA genotype relative to AT + TT genotypes (P< 0.01). Our results confirmed that, in addition to heroin consumption, the SNP rs6943555 of AUTS2 may also play an important role in the etiology of heroin dependence.