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| Content Provider | PubMed Central |
|---|---|
| Author | Shabalina, Svetlana A. Zaykin, Dmitri V. Gris, Pavel Ogurtsov, Aleksey Y. Gauthier, Josee Shibata, Kyoko Tchivileva, Inna E. Belfer, Inna Mishra, Bikashkumar Kiselycznyk, Carly Wallace, Margaret R. Staud, Roland Spiridonov, Nikolay A. Max, Mitchell B. Goldman, David Fillingim, Roger B. Maixner, William Diatchenko, Luda |
| Copyright Year | 2009 |
| Abstract | The μ-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. |
| Related Links | http://dx.doi.org/10.1093/hmg/ddn439 |
| Ending Page | 1051 |
| Page Count | 15 |
| Starting Page | 1037 |
| File Format | |
| ISSN | 09646906 |
| e-ISSN | 14602083 |
| Journal | Human Molecular Genetics |
| Issue Number | 6 |
| Volume Number | 18 |
| Language | English |
| Publisher | Oxford University Press |
| Publisher Date | 2009-01-01 |
| Access Restriction | Open |
| Rights Holder | Oxford University Press |
| Subject Keyword | Genetics(clinical) Genetics Molecular Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Molecular Biology Genetics (clinical) |
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