title: A molecular prospective provides new insights into implication of PDYN and OPRK1 genes in alcohol dependence.
abstract: Single nucleotide polymorphisms (SNPs) both in coding and non-coding regions govern gene functions prompting differential vulnerability to diseases, heterogeneous response to pharmaceutical regimes and environmental anomalies. These genetic variations, SNPs, may alter an individual׳s susceptibility for alcohol dependence by remodeling DNA-protein interaction patterns in prodynorphin (PDYN) and the κ-opioid receptor (OPRK1) genes. In order to elaborate the underlying molecular mechanism behind these susceptibility differences we used bioinformatics tools to retrieve differential DNA-protein interactions at PDYN and OPRK1 SNPs significantly associated with alcohol dependence. Our results show allele-specific DNA-protein interactions depicting allele-specific mechanisms implicated in differential regulation of gene expression. Several transcription factors, for instance, VDR, RXR-alpha, NFYA, CTF family, USF-1, USF2, ER, AR and predominantly SP family show an allele-specific binding affinity with PDYN gene; likewise, GATA, TBP, AP-1, USF-2, C/EBPbeta, Cart-1 and ER interact with OPRK1 SNPs on intron 2 in an allele-specific manner. In a nutshell, transition of a single nucleotide may modify differential DNA-protein interactions at OPRK1 and PDYN׳s SNPs, significantly associated with pathology that may lead to altered individual vulnerability for alcohol dependence.
authors.affiliation: National Center for Bioinformatics, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Faisal
authors.affiliation: Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors.forename: Durdana
authors.initials: D
authors.lastname: Waseem
authors.affiliation: Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, Pakistan.
authors.forename: Humaira
authors.initials: H
authors.lastname: Ismatullah
authors.affiliation: Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: mm_taqi@qau.edu.pk.
authors.forename: Malik Mumtaz
authors.initials: MM
authors.lastname: Taqi
mesh_terms: D000437:Alcoholism / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology; D030541:Databases, Genetic; D004745:Enkephalins / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics*; D017473:Receptors, Opioid, kappa / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D020506:Untranslated Regions / Q000235:genetics
chemical_list: D004745:Enkephalins; C515653:OPRK1 protein, human; D011498:Protein Precursors; D017473:Receptors, Opioid, kappa; D014157:Transcription Factors; D020506:Untranslated Regions; C033660:preproenkephalin
keywords: Alcohol addiction; Allele-specific interactions; Prodynorphin (PDYN); Transcription factors; κ-opioid receptor (OPRK1)