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PMID: 18195715 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Genotype patterns that contribute to increased risk for or protection from developing heroin addiction.

Molecular psychiatry ·Vol. 13 ·No. 4 ·2008-04-00 ·Pages 417-28

Nielsen DA, Ji F, Yuferov V, Ho A, Chen A, Levran O, Ott J, Kreek MJ

Abstract

A genome-wide association study was conducted using microarray technology to identify genes that may be associated with the vulnerability to develop heroin addiction, using DNA from 104 individual former severe heroin addicts (meeting Federal criteria for methadone maintenance) and 101 individual control subjects, all Caucasian. Using separate analyses for autosomal and X chromosomal variants, we found that the strongest associations of allele frequency with heroin addiction were with the autosomal variants rs965972, located in the Unigene cluster Hs.147755 (experiment-wise q=0.053), and rs1986513 (q=0.187). The three variants exhibiting the strongest association with heroin addiction by genotype frequency were rs1714984, located in an intron of the gene for the transcription factor myocardin (P=0.000022), rs965972 (P=0.000080) and rs1867898 (P=0.000284). One genotype pattern (AG-TT-GG) was found to be significantly associated with developing heroin addiction (odds ratio (OR)=6.25) and explained 27% of the population attributable risk for heroin addiction in this cohort. Another genotype pattern (GG-CT-GG) of these variants was found to be significantly associated with protection from developing heroin addiction (OR=0.13), and lacking this genotype pattern explained 83% of the population attributable risk for developing heroin addiction. Evidence was found for involvement of five genes in heroin addiction, the genes coding for the mu opioid receptor, the metabotropic receptors mGluR6 and mGluR8, nuclear receptor NR4A2 and cryptochrome 1 (photolyase-like). This approach has identified several new genes potentially associated with heroin addiction and has confirmed the role of OPRM1 in this disease.

MeSH Terms
Chromosomes, Human, X Cryptochromes DNA-Binding Proteins/genetics Female Flavoproteins/genetics Gene Frequency Genetic Predisposition to Disease Genetic Testing Genetic Variation Genotype Heroin Dependence Humans Linkage Disequilibrium Male Nuclear Proteins/genetics Nuclear Receptor Subfamily 4, Group A, Member 2 Oligonucleotide Array Sequence Analysis/methods Receptors, Metabotropic Glutamate/genetics Receptors, Opioid, mu/genetics Trans-Activators/genetics Transcription Factors/genetics Whites
Chemicals
Cryptochromes DNA-Binding Proteins Flavoproteins NR4A2 protein, human Nuclear Proteins Nuclear Receptor Subfamily 4, Group A, Member 2 OPRM1 protein, human Receptors, Metabotropic Glutamate Receptors, Opioid, mu Trans-Activators Transcription Factors metabotropic glutamate receptor 6 metabotropic glutamate receptor 8 myocardin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Nielsen D A
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10065, USA. nielsen@rockefeller.edu
Ji F
Yuferov V
Ho A
Chen A
Levran O
Ott J
Kreek M J
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Article Info
Journal
Molecular psychiatry
Abbr.
Mol Psychiatry
ISSN
1476-5578
DOI
10.1038/sj.mp.4002147
Email
nielsen@rockefeller.edu
Published
2008-04-00
Epub
2008-00-15
Pages
417-28
Language
English
Region
England
NLM ID
9607835
PMCID
PMC3810149
Subset
IM
Grants
NIDA NIH HHS · K05 DA000049 · United States
NIDA NIH HHS · P60 DA005130 · United States
PHS HHS · P60-05130 · United States
PHS HHS · R01-44292 · United States
NCRR NIH HHS · UL1RR024143 · United States
NCRR NIH HHS · UL1 RR024143 · United States
PHS HHS · K05-00049 · United States
External Links
PubMed source DOI: 10.1038/sj.mp.4002147 PMC Full Text View journal details
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