title: An Information Theoretical Study of the Epistasis Between the CNR1 1359 G/A Polymorphism and the Taq1A and Taq1B DRD2 Polymorphisms: Assessing the Susceptibility to Cannabis Addiction in a Turkish Population.
abstract: Addiction is a complex, multi-factorial disease, and thus, analyzing genetic variants at multiple loci and gene-gene interactions among them (epistasis) can provide crucial clues about causative factors of addiction which cannot be detected with single-nucleotide polymorphism (SNP) association studies. In this study, we discuss the interaction between the 1359 G/A polymorphism of the CNR1 gene and the DRD2 gene polymorphisms and the net effect of any possible epistasis on the cannabis addiction phenotype in a Turkish population. Using bivariate synergy and mutual information concepts as a means of capturing the magnitude of interaction between marker pairs, the present study not only confirms the A1 marker allele as a risk factor but also reveals a finer-grained association between A and B markers which manifests itself both as a preventive and a risk factor. Our results indicate that the increased phenotype of cases require an individual to be either heterozygous at both loci or homozygous at locus B with homozygous risk factor A1A1 present. We hypothesize that overlapping expressions of CB1 and D2R is the cause of CB1-D2R interactions in cases of substance abuse and the different polymorphisms of CNR1 and DRD2 genes may have decisive roles in the nature of these interactions in terms of promoting or alleviating the cannabis addiction risk factor of the individual.
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey. aybaransel@yahoo.com.
authors.forename: Aysun Baransel
authors.initials: AB
authors.lastname: Isir
authors.affiliation: Department of Computer Engineering, University of Turkish Aeronautical Association, Ankara, Turkey.
authors.forename: Cesur
authors.initials: C
authors.lastname: Baransel
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey.
authors.forename: Muradiye
authors.initials: M
authors.lastname: Nacak
mesh_terms: D016022:Case-Control Studies; D004843:Epistasis, Genetic; D006579:Heterozygote; D006801:Humans; D002189:Marijuana Abuse / Q000235:genetics*; D008957:Models, Genetic; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*
chemical_list: C571130:CNR1 protein, human; C581293:DRD2 protein, human; D043884:Receptor, Cannabinoid, CB1; D017448:Receptors, Dopamine D2
keywords: CNR1 1359 G/A polymorphism; Cannabis addiction; Epistasis study; Taq1A and Taq1B DRD2 polymorphisms; Turkish population
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