title: Analyzing Interaction of μ-, δ- and κ-opioid Receptor Gene Variants on Alcohol or Drug Dependence Using a Pattern Discovery-based Method.
abstract: BACKGROUND
  Polymorphisms in the μ-, δ- and κ-opioid receptor genes (OPRM1,OPRD1andOPRK1) have been reported to be associated with substance (alcohol or drug) dependence. The influence of an individual gene on a disease trait should be more evident when analyzed in the context of gene-gene interactions. Thus, we assessed the joint effect of variants in these three opioid receptor genes on alcohol, cocaine, or opioid dependence.
  
  
  METHODS
  Genotype data for 13OPRM1Single Nucleotide Polymorphisms (SNPs), 11OPRD1SNPs and sevenOPRK1SNPs were obtained from 382 European Americans (EAs) affected with substance dependence [among them, 318 with Alcohol Dependence (AD), 171 with Cocaine Dependence (CD), and 91 with Opioid Dependence (OD)] and 338 EA control subjects. We assessed the joint effect ofOPRM1,OPRD1andOPRK1variants on AD, CD, or OD using a pattern discovery-based association test. Specific marker patterns (consisting of alleles ofOPRM1,OPRD1andOPRK1) that were significantly more frequent in AD, CD, or OD cases than in controls were identified.
  
  
  RESULTS
  12 significant patterns in the AD dataset, four significant patterns in the CD dataset, and 18 significant patterns in the OD dataset were identified. Moreover, the significance of most marker patterns was due primarily toOPRM1variants and, to a lesser degree,OPRD1variants.
  
  
  CONCLUSIONS
  Our findings suggest that variation in the above three opioid receptor genes can jointly influence the vulnerability of individuals to alcohol or drug dependence. Evidence provided by this study also supports previous biological findings that the interaction of the three opioid receptors can modulate the action of opioid and non-opioid drugs and alcohol.
authors.affiliation: Department of Computational Genetics, High Throughput Biology Inc., Summit, NJ, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA ; VA Connecticut Healthcare System, West Haven Campus, CT, USA.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhang
keywords: Case-control genetic association study; Gene-gene interaction; Opioid receptor genes; Pattern discovery-based association test