Research Article
Analyzing Interaction of μ-, δ- and κ-opioid Receptor Gene Variants on Alcohol or Drug Dependence Using a Pattern Discovery-based Method
Zhong Li1 and Huiping Zhang2,3*1Department of Computational Genetics, High Throughput Biology Inc., Summit, NJ, USA
2Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
3VA Connecticut Healthcare System, West Haven Campus, CT, USA
- *Corresponding Author:
- Huiping Zhang
Department of Psychiatry
Yale University School of Medicine
VA Medical Center/116A2, 950 Campbell Avenue
West Haven, CT 06516, USA
Tel: (203)932-5711 ext. 5245
Fax: (203)937-4741
E-mail: huiping.zhang@yale.edu
Received April 08, 2013; Accepted May 03, 2013; Published May 14, 2013
Citation: Li Z, Zhang H (2013) Analyzing Interaction of µ-, δ- and κ-opioid Receptor Gene Variants on Alcohol or Drug Dependence Using a Pattern Discovery-based Method. J Addict Res Ther S7:007. doi:10.4172/2155-6105.S7-007
Copyright: © 2013 Li Z, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Polymorphisms in the μ-, δ- and κ-opioid receptor genes (OPRM1, OPRD1 and OPRK1) 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 13 OPRM1 Single Nucleotide Polymorphisms (SNPs), 11 OPRD1 SNPs and seven OPRK1 SNPs 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 of OPRM1, OPRD1 and OPRK1 variants on AD, CD, or OD using a pattern discovery-based association test. Specific marker patterns (consisting of alleles of OPRM1, OPRD1 and OPRK1) 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 to OPRM1 variants and, to a lesser degree, OPRD1 variants.
Conclusion: 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.