title: Influence of OPRM1 Asn40Asp variant (A118G) on [11C]carfentanil binding potential: preliminary findings in human subjects.
abstract: The Asn40Asp variant (A118G) of the μ opioid receptor (OPRM1) gene is thought to contribute to the development and treatment of alcohol dependence. Employing positron emission tomography (PET), we first examined whether the single nucleotide polymorphism (SNP) modifies binding potential (BP(ND)) of the μ-selective ligand [(11)C]carfentanil in healthy control (Con) and 5-d abstinent alcohol-dependent (AD) subjects (unblocked basal scan). Second, we examined whether the allelic variants were associated with differences in OPRM1 occupancy by naltrexone (50 mg) in AD subjects. Con and AD carriers of the G allele (AG) had lower global BP(ND) at the basal scan than subjects homozygous for the A allele (AA). In AD subjects, naltrexone occupancy was slightly higher in AG subjects (98.9%) compared to AA subjects (93.1%), but this was not significant. We are the first to demonstrate using PET in healthy normal and AD subjects that the A118G SNP alters OPRM1 availability.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Elise M
authors.initials: EM
authors.lastname: Weerts
authors.forename: Mary E
authors.initials: ME
authors.lastname: McCaul
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kuwabara
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Yang
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Xu
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.forename: J James
authors.initials: JJ
authors.lastname: Frost
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.forename: Gary S
authors.initials: GS
authors.lastname: Wand
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000235:genetics / Q000378:metabolism; D001216:Asparagine / Q000235:genetics*; D001224:Aspartic Acid / Q000235:genetics*; D002250:Carbon Radioisotopes / Q000378:metabolism; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000378:metabolism; D014644:Genetic Variation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D001224:Aspartic Acid; D001216:Asparagine; C017114:carfentanil; D005283:Fentanyl