title: Increased OPRM1 DNA methylation in lymphocytes of methadone-maintained former heroin addicts.
abstract: The mu-opioid receptor is the site of action of opiates and opioids. We examined whether there are differences in cytosine:guanine (CpG) dinucleotide methylation in the OPRM1 promoter between former heroin addicts and controls. We analyzed methylation at 16 CpG dinucleotides in DNA obtained from lymphocytes of 194 Caucasian former severe heroin addicts stabilized in methadone maintenance treatment and 135 Caucasian control subjects. Direct sequencing of bisulfite-treated DNA showed that the percent methylation at two CpG sites was significantly associated with heroin addiction. The level of methylation at the -18 CpG site was 25.4% in the stabilized methadone-maintained former heroin addicts and 21.4% in controls (p=0.0035, generalized estimating equations (GEE); p=0.0077, t-test; false discovery rate (FDR)=0.048), and the level of methylation at the +84 CpG dinucleotide site was 7.4% in cases and 5.6% in controls (p=0.0095, GEE; p=0.0067, t-test; FDR=0.080). Both the -18 and the +84 CpG sites are located in potential Sp1 transcription factor-binding sites. Methylation of these CpG sites may lead to reduced OPRM1 expression in the lymphocytes of these former heroin addicts.
authors.affiliation: Laboratory of the Biology of the Addictive Diseases, The Rockefeller University, New York, NY 10065, USA. nielsen@rockefeller.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Nielsen
authors.forename: Vadim
authors.initials: V
authors.lastname: Yuferov
authors.forename: Sara
authors.initials: S
authors.lastname: Hamon
authors.forename: Colin
authors.initials: C
authors.lastname: Jackson
authors.forename: Ann
authors.initials: A
authors.lastname: Ho
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
authors.forename: Mary Jeanne
authors.initials: MJ
authors.lastname: Kreek
mesh_terms: D001483:Base Sequence; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006556:Heroin Dependence / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008691:Methadone / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012984:Software; D044465:White People / Q000235:genetics
chemical_list: C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D008691:Methadone