Li Yunxiao, Qiao Xiaomeng, Yin Fangyuan, Guo Hao, Huang Xin, Lai Jianghua, Wei Shuguang
College of Forensic Science, Xi'an Jiaotong University, Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an, PR China.
Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, PR China.
PLoS One. 2016 Sep 27;11(9):e0163668. doi: 10.1371/journal.pone.0163668. eCollection 2016.
Recent studies have shown that variants in FAT atypical cadherin 3 (FAT3), kinectin 1 (KTN1), discs large homolog2 (DLG2) and deleted in colorectal cancer (DCC) genes influence the structure of the human mesolimbic reward system. We conducted a systematic analysis of the potential functional single nucleotide polymorphisms (SNPs) in these genes associated with heroin addiction. We scanned the functional regions of these genes and identified 20 SNPs for genotyping by using the SNaPshot method. A total of 1080 samples, comprising 523 cases and 557 controls, were analyzed. We observed that DCC rs16956878, rs12607853, and rs2292043 were associated with heroin addiction. The T alleles of rs16956878 (p = 0.0004) and rs12607853 (p = 0.002) were significantly enriched in the case group compared with the controls. A lower incidence of the C allele of rs2292043 (p = 0.002) was observed in the case group. In block 2 of DCC (rs2292043-rs12607853-rs16956878), the frequency of the T-T-T haplotype was significantly higher in the case group than in the control group (p = 0.024), and fewer C-C-C haplotypes (p = 0.006) were detected in the case group. DCC may be an important candidate gene in heroin addiction, and rs16956878, rs12607853, and rs2292043 may be risk factors, thereby providing a basis for further genetic and biological research.
近期研究表明，FAT非典型钙黏蛋白3（FAT3）、驱动蛋白连接蛋白1（KTN1）、盘状大同源蛋白2（DLG2）和结直肠癌缺失基因（DCC）的变异会影响人类中脑边缘奖赏系统的结构。我们对这些与海洛因成瘾相关基因中的潜在功能性单核苷酸多态性（SNP）进行了系统分析。我们扫描了这些基因的功能区域，并使用SNaPshot方法鉴定了20个SNP进行基因分型。总共分析了1080个样本，包括523例病例和557例对照。我们观察到DCC基因的rs16956878、rs12607853和rs2292043与海洛因成瘾相关。与对照组相比，rs16956878（p = 0.0004）和rs12607853（p = 0.002）的T等位基因在病例组中显著富集。在病例组中观察到rs2292043的C等位基因发生率较低（p = 0.002）。在DCC基因的第2个区域（rs2292043 - rs12607853 - rs16956878），病例组中T - T - T单倍型的频率显著高于对照组（p = 0.024），且在病例组中检测到的C - C - C单倍型较少（p = 0.006）。DCC可能是海洛因成瘾的一个重要候选基因，而rs16956878、rs12607853和rs2292043可能是危险因素，从而为进一步的遗传和生物学研究提供了依据。
