title: 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.
authors.affiliation: Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Yun-Hsiang
authors.initials: YH
authors.lastname: Chen
authors.forename: Ding-Lieh
authors.initials: DL
authors.lastname: Liao
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Lai
authors.forename: Chia-Hsiang
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000328:Adult; D044466:Asian People; D016022:Case-Control Studies; D002461:Cell Line, Transformed; D003598:Cytoskeletal Proteins; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006556:Heroin Dependence / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D013624:Taiwan; D014157:Transcription Factors
chemical_list: C554283:AUTS2 protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins; D014157:Transcription Factors