| Title | Single-nucleotide polymorphism (A118G) in exon 1 of OPRM1 gene causes alteration in downstream signaling by mu-opioid receptor and may contribute to the genetic risk for addiction. | | Author(s) | Deb I, Chakraborty J, Gangopadhyay PK, Choudhury SR, Das S | | Institution | Neurobiology Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India. | | Source | J Neurochem 2009 Nov 4. | | Abstract | The opioid receptor mu1 (OPRM1) mediates the action of morphine. Although genetic background plays an important role in the susceptibility towards abuse of drugs as evident from familial, adoption and twin studies, association of specific single nucleotide polymorphisms (SNP) of OPRM1 gene with narcotic addiction is to be established. Here we demonstrate the involvement of A118G polymorphism of exon1 of human OPRM1 gene (hOPRM1), with heroin and alcohol addiction, in a population in eastern India. Statistical analysis exhibited a significant association of G allele with both heroin and alcohol addiction with a risk factor of P(trend)<0.05. The functional significance of G allele in A118G SNP was evaluated by studying the regulation of protein kinase A (PKA), pCREB and pERK1/2 by morphine in Neuro 2A cells, stably transfected with either wild type or A118G mutant hOPRM1. Unlike acute morphine treatment, both chronic morphine exposure and withdrawal precipitated by naloxone were differentially regulated by A118 and G118 receptor isoforms when both PKA and pERK1/2 activities were compared. Results suggest that the association of A118G polymorphism to heroin and alcohol addiction may be due to the altered regulation of PKA and pERK1/2 during opioid and alcohol exposures. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19891732 |
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