Genetic analysis of AUTS2 as a susceptibility gene of heroin dependence

Abstract

Background: Both alcoholism and heroin dependence are common substance use disorders with a high genetic basis. A recent genetic study reported that the autism susceptibility candidate 2 gene (AUTS2) was involved in regulating the alcohol drinking behavior. In our previous total gene expression profiling study, we found that the AUTS2 transcript was significantly down-regulated in lymphoblastoid cell lines (LCL) in heroin dependent individuals compared with control subjects, which prompted us to investigate whether AUTS2 is associated with heroin dependence.

Methods: We compared the AUTS2 transcript level of LCL between 124 heroin dependent males and 116 control males using real-time quantitative PCR, and conducted a genetic association study of the rs6943555 of AUTS2 with heroin dependence using a sample of 546 heroin dependent males and 373 control males.

Results: We first verified that the average transcript level of AUTS2 in the heroin dependent group was significantly lower than that in the control group (p=0.017). In the genetic association analysis, we found that AA homozygotes of rs6943555 were significantly over-represented in the heroin dependent subjects compared with the control subjects (odds ratio=1.7, 95% confidence interval: 1.08-2.74, p=0.017). Analyzing the sample from the AUTS2 transcript experiment, we found that AA carriers (n=19) had significantly lower AUTS2 mRNA levels in their LCL compared to TT carriers (n=97, p=0.002) and AT carriers (n=91, p=0.005).

Conclusions: Our data indicate that the AUTS2 gene might be associated with heroin dependence, and reduced AUTS2 gene expression might confer increased susceptibility to heroin dependence.