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Expansion of the human mu-opioid receptor gene architecture: novel functional variants.

Publication ,  Journal Article
Shabalina, SA; Zaykin, DV; Gris, P; Ogurtsov, AY; Gauthier, J; Shibata, K; Tchivileva, IE; Belfer, I; Mishra, B; Kiselycznyk, C; Wallace, MR ...
Published in: Hum Mol Genet
March 15, 2009

The mu-opioid receptor (OPRM1) is the principal receptor target for both endogenous and exogenous opioid analgesics. There are substantial individual differences in human responses to painful stimuli and to opiate drugs that are attributed to genetic variations in OPRM1. In searching for new functional variants, we employed comparative genome analysis and obtained evidence for the existence of an expanded human OPRM1 gene locus with new promoters, alternative exons and regulatory elements. Examination of polymorphisms within the human OPRM1 gene locus identified strong association between single nucleotide polymorphism (SNP) rs563649 and individual variations in pain perception. SNP rs563649 is located within a structurally conserved internal ribosome entry site (IRES) in the 5'-UTR of a novel exon 13-containing OPRM1 isoforms (MOR-1K) and affects both mRNA levels and translation efficiency of these variants. Furthermore, rs563649 exhibits very strong linkage disequilibrium throughout the entire OPRM1 gene locus and thus affects the functional contribution of the corresponding haplotype that includes other functional OPRM1 SNPs. Our results provide evidence for an essential role for MOR-1K isoforms in nociceptive signaling and suggest that genetic variations in alternative OPRM1 isoforms may contribute to individual differences in opiate responses.

Duke Scholars

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

March 15, 2009

Volume

18

Issue

6

Start / End Page

1037 / 1051

Location

England

Related Subject Headings

  • Receptors, Opioid, mu
  • RNA Splicing
  • Protein Isoforms
  • Polymorphism, Single Nucleotide
  • Pain
  • Nucleic Acid Conformation
  • Molecular Sequence Data
  • Mice
  • Introns
  • Humans
 

Citation

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Shabalina, S. A., Zaykin, D. V., Gris, P., Ogurtsov, A. Y., Gauthier, J., Shibata, K., … Diatchenko, L. (2009). Expansion of the human mu-opioid receptor gene architecture: novel functional variants. Hum Mol Genet, 18(6), 1037–1051. https://doi.org/10.1093/hmg/ddn439
Shabalina, Svetlana A., Dmitri V. Zaykin, Pavel Gris, Aleksey Y. Ogurtsov, Josee Gauthier, Kyoko Shibata, Inna E. Tchivileva, et al. “Expansion of the human mu-opioid receptor gene architecture: novel functional variants.Hum Mol Genet 18, no. 6 (March 15, 2009): 1037–51. https://doi.org/10.1093/hmg/ddn439.
Shabalina SA, Zaykin DV, Gris P, Ogurtsov AY, Gauthier J, Shibata K, et al. Expansion of the human mu-opioid receptor gene architecture: novel functional variants. Hum Mol Genet. 2009 Mar 15;18(6):1037–51.
Shabalina, Svetlana A., et al. “Expansion of the human mu-opioid receptor gene architecture: novel functional variants.Hum Mol Genet, vol. 18, no. 6, Mar. 2009, pp. 1037–51. Pubmed, doi:10.1093/hmg/ddn439.
Shabalina SA, Zaykin DV, Gris P, Ogurtsov AY, Gauthier J, Shibata K, Tchivileva IE, Belfer I, Mishra B, Kiselycznyk C, Wallace MR, Staud R, Spiridonov NA, Max MB, Goldman D, Fillingim RB, Maixner W, Diatchenko L. Expansion of the human mu-opioid receptor gene architecture: novel functional variants. Hum Mol Genet. 2009 Mar 15;18(6):1037–1051.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

March 15, 2009

Volume

18

Issue

6

Start / End Page

1037 / 1051

Location

England

Related Subject Headings

  • Receptors, Opioid, mu
  • RNA Splicing
  • Protein Isoforms
  • Polymorphism, Single Nucleotide
  • Pain
  • Nucleic Acid Conformation
  • Molecular Sequence Data
  • Mice
  • Introns
  • Humans