Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Human molecular genetics, 2009-03, Vol.18 (6), p.1037-1051

Ort / Verlag

Oxford: Oxford University Press

Erscheinungsjahr

2009

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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.