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Association of polymorphisms of the cannabinoid receptor (CNR1) and fatty acid amide hydrolase (FAAH) genes with heroin addiction: impact of long repeats of CNR1

The Pharmacogenomics Journal volume 10, pages 232–242 (2010)Cite this article

Abstract

Alterations in expression of a cannabinoid receptor (CNR1, CB1), and of fatty acid amide hydrolase (FAAH) that degrades endogenous ligands of CB1, may contribute to the development of addiction. The 385C>A in the FAAH gene and six polymorphisms of CNR1 were genotyped in former heroin addicts and control subjects (247 Caucasians, 161 Hispanics, 179 African Americans and 19 Asians). In Caucasians, long repeats (⩾14) of 18087–18131(TAA)8−17 were associated with heroin addiction (P=0.0102). Across three ethnicities combined, a highly significant association of long repeats with heroin addiction was found (z=3.322, P=0.0009). Point-wise significant associations of allele 1359A (P=0.006) and genotype 1359AA (P=0.034) with protection from heroin addiction were found in Caucasians. Also in Caucasians, the genotype pattern, 1359G>A and −6274A>T, was significantly associated with heroin addiction experiment wise (P=0.0244). No association of FAAH 385C>A with heroin addiction was found in any group studied.

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Acknowledgements

We thank Dr Vadim Yuferov, Dr David Nielsen, Dr Orna Levran and the late Dr K Steven LaForge for comments and a critical review of the paper. We thank Matthew Swift and Johannes Adomako-Mensah for technical assistance. This work was supported by NIH-NIDA Grant P60-DA05130 (MJK), NSFC Grant 30730057 from the Chinese Government (JO) and NIH/NCRR-CTSA UL1-RR024143 (The Rockefeller University Center for Clinical and Translational Science).

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Authors and Affiliations

  1. Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY, USA

    D Proudnikov, T Kroslak, M Randesi, A Ho & M J Kreek

  2. Division of Neurology, The Scripps Research Institute, La Jolla, CA, USA

    J C Sipe

  3. Laboratory of Statistical Genetics, The Rockefeller University, New York, NY, USA

    D Li, S Hamon & J Ott

  4. Department of Psychiatry, Yale University, New Haven, CT, USA

    D Li

  5. Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China

    J Ott

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Proudnikov, D., Kroslak, T., Sipe, J. et al. Association of polymorphisms of the cannabinoid receptor (CNR1) and fatty acid amide hydrolase (FAAH) genes with heroin addiction: impact of long repeats of CNR1. Pharmacogenomics J 10, 232–242 (2010). https://doi.org/10.1038/tpj.2009.59

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