Abstract
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.
Highlights
Heroin addiction is a chronic brain disease characterized by compulsive drug-seeking, drug abuse, physical dependence, tolerance, and relapse [1]
The rs17128657 single nucleotide polymorphisms (SNPs) statistically deviated from Hardy-Weinberg equilibrium (HWE) (p = 0.028)
Five blocks were identified in the linkage disequilibrium (LD) analysis of the case and control data
Summary
Heroin addiction is a chronic brain disease characterized by compulsive drug-seeking, drug abuse, physical dependence, tolerance, and relapse [1]. Heroin is one of the most commonly used drugs in China. At the end of 2014, a total of 2.955 million drug addicts were registered in China. Opioid drug addicts numbered 1.458 million, 49.3% of whom were heroin users. A total of 9.3 tons of heroin were seized in 2014. The direct economic losses resulting from drug addiction approach CNY 500 billion every year, representing a substantial economic burden to PLOS ONE | DOI:10.1371/journal.pone.0163668. The direct economic losses resulting from drug addiction approach CNY 500 billion every year, representing a substantial economic burden to PLOS ONE | DOI:10.1371/journal.pone.0163668 September 27, 2016
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