Comput. Biol. Med. - A molecular prospective provides new insights into implication of PDYN and OPRK1 genes in alcohol dependence.

Tópicos

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Resumo

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 individuals susceptibility for alcohol dependence by remodeling DNA-protein interaction patterns in prodynorphin (PDYN) and the -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 PDYNs SNPs, significantly associated with pathology that may lead to altered individual vulnerability for alcohol dependence.

Resumo Limpo

singl nucleotid polymorph snps code noncod region govern gene function prompt differenti vulner diseas heterogen respons pharmaceut regim environment anomali genet variat snps may alter individu suscept alcohol depend remodel dnaprotein interact pattern prodynorphin pdyn opioid receptor oprk gene order elabor under molecular mechan behind suscept differ use bioinformat tool retriev differenti dnaprotein interact pdyn oprk snps signific associ alcohol depend result show allelespecif dnaprotein interact depict allelespecif mechan implic differenti regul gene express sever transcript factor instanc vdr rxralpha nfya ctf famili usf usf er ar predomin sp famili show allelespecif bind affin pdyn gene likewis gata tbp ap usf cebpbeta cart er interact oprk snps intron allelespecif manner nutshel transit singl nucleotid may modifi differenti dnaprotein interact oprk pdyn snps signific associ patholog may lead alter individu vulner alcohol depend

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