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.
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| 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.
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| Creator |
Deb, Ishani
Chakraborty, J Gangopadhyay, Prasanta K Roychoudhury, Susanta Das, Sumantra |
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| Subject |
Cell Biology & Physiology
Molecular & Human Genetics |
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| Description |
The opioid receptor mu1 (OPRM1) mediates the action of
morphine. Although genetic background plays an important
role in the susceptibility toward abuse of drugs as evident from
familial, adoption and twin studies, association of specific
single-nucleotide polymorphisms 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 Ptrend < 0.05. The functional
significance of G allele in A118G single-nucleotide polymorphisms
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
because of the altered regulation of PKA and pERK1/2 during
opioid and alcohol exposures.
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| Publisher |
Blackwell Publishing
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| Date |
2010
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1064/1/2010%2DJN.pdf
Deb, Ishani and Chakraborty, J and Gangopadhyay, Prasanta K and Roychoudhury, Susanta and Das, Sumantra (2010) 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. Journal of Neurochemistry, 112. pp. 486-496. |
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| Relation |
http://dx.doi.org/10.1111/j.1471-4159.2009.06472.x
http://www.eprints.iicb.res.in/1064/ |
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