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The Evidence for the Contribution of the Autism Susceptibility Candidate 2 (AUTS2) Gene in Heroin Dependence Susceptibility

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Abstract

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.

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Acknowledgments

This research was partially supported by the Science and Technology Bureau Projects of Xi’an (SF1210 (1-d)), the Research and Development Foundation of Science and Technology of Shaanxi Province and the National Science Foundation of China (#NSFC 31100900), and Postdoctoral Science Foundation of China (137033). The funding sources had input into the design of this study, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the paper for publication.

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Authors and Affiliations

  1. Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University College of Forensic Science, Xi’an Jiaotong University, Xi’an, Shaanxi, 710049, People’s Republic of China

    Wei Dang, Yong-Sheng Zhu & Xiao-Yun Lu

  2. The Sixth Ward, Xi’an Mental Health Center, Xi’an, Shannxi, China

    Wei Dang

  3. Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China

    Qian Zhang & Yong-Sheng Zhu

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  1. Wei Dang
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  2. Qian Zhang
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  3. Yong-Sheng Zhu
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  4. Xiao-Yun Lu
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Corresponding authors

Correspondence to Yong-Sheng Zhu or Xiao-Yun Lu.

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Wei Dang and Qian Zhang contributed equally to this work.

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Dang, W., Zhang, Q., Zhu, YS. et al. The Evidence for the Contribution of the Autism Susceptibility Candidate 2 (AUTS2) Gene in Heroin Dependence Susceptibility. J Mol Neurosci 54, 811–819 (2014). https://doi.org/10.1007/s12031-014-0421-5

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  • DOI: https://doi.org/10.1007/s12031-014-0421-5

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