Ethnic diversity of DNA methylation in the OPRM1 promoter region in lymphocytes of heroin addicts.
The mu-opioid receptor is the site of action of many endogenous opioids as well as opiates. We hypothesize that differences in DNA methylation of specific CpG dinucleotides between former severe heroin addicts in methadone maintenance treatment and control subjects will depend, in part, upon ethnicity. DNA methylation analysis of the mu-opioid receptor gene (OPRM1) promoter region was performed on African-Americans (118 cases, 80 controls) and Hispanics (142 cases, 61 controls) and these were compared with a similar Caucasian cohort from our earlier study. In controls, a higher methylation level was found in the African-Americans compared with the Hispanics or Caucasians. Significant experiment-wise differences in methylation levels were found at the -25 and +12 CpG sites in the controls among the three ethnicities. The overall methylation level of the CpG sites were significantly higher in the former heroin addicts when compared with the controls (point-wise P = 0.0457). However, in the African-Americans, the degree of methylation was significantly decreased experiment-wise in the former heroin addicts at the +12 CpG site (P = 0.0032, Bonferroni corrected general estimating equations). In Hispanics, the degree of methylation was increased in the former heroin addicts at the -25 (P < 0.001, experiment-wise), -14 (P = 0.001, experiment-wise), and +27 (P < 0.001, experiment-wise) CpG sites. These changes in methylation of the OPRM1 promoter region may lead to altered expression of the mu-opioid receptor gene in the lymphocytes of former heroin addicts who are stabilized in methadone maintenance treatment.
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, Box 171, 1230 York Avenue, New York 10065, USA.
David A
DA
Nielsen
Sara
S
Hamon
Vadim
V
Yuferov
Colin
C
Jackson
Ann
A
Ho
Jurg
J
Ott
Mary Jeanne
MJ
Kreek
D001741:Black or African American / Q000235:genetics; D019175:DNA Methylation; D015226:Dinucleoside Phosphates / Q000378:metabolism; D005006:Ethnicity / Q000235:genetics*; D006556:Heroin Dependence / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics
D015226:Dinucleoside Phosphates; D017450:Receptors, Opioid, mu; C485764:OPRM1 protein, human; C015772:CpG dinucleotide