CNR1 gene polymorphisms in addictive disorders: a systematic review and a meta-analysis

Authors

  • Amine Benyamina,

    Corresponding author
    1. INSERM U669, Paris, France,
    2. AP-HP, Paul Brousse Hospital, Centre for Training, Research and Treatment in Addictions, Villejuif, France,
    3. University Paris-Sud, UMR-S0669, Kremlin-Bicêtre, France,
    4. Laboratoire de Physiopathologie des Maladies Psychiatriques, Centre de psychiatrie et Neurosciences, INSERM U894, Paris, France and
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  • Oussama Kebir,

    1. Laboratoire de Physiopathologie des Maladies Psychiatriques, Centre de psychiatrie et Neurosciences, INSERM U894, Paris, France and
    2. Faculty of Medicine Paris Descartes, University Paris Descartes, Paris, France
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  • Lisa Blecha,

    1. INSERM U669, Paris, France,
    2. AP-HP, Paul Brousse Hospital, Centre for Training, Research and Treatment in Addictions, Villejuif, France,
    3. University Paris-Sud, UMR-S0669, Kremlin-Bicêtre, France,
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  • Michel Reynaud,

    1. INSERM U669, Paris, France,
    2. AP-HP, Paul Brousse Hospital, Centre for Training, Research and Treatment in Addictions, Villejuif, France,
    3. University Paris-Sud, UMR-S0669, Kremlin-Bicêtre, France,
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  • Marie-Odile Krebs

    1. Laboratoire de Physiopathologie des Maladies Psychiatriques, Centre de psychiatrie et Neurosciences, INSERM U894, Paris, France and
    2. Faculty of Medicine Paris Descartes, University Paris Descartes, Paris, France
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Amine Benyamina, Hôpital Paul Brousse, 12-14 Avenue Paul Vaillant Couturier, 94804 Villejuif Cedex, France. E-mail: amine.benyamina@pbr.aphp.fr

ABSTRACT

The aim of the present work was to systematically review all association studies of cannabis receptor 1 (CNR1) polymorphisms with dependence syndrome and to perform a meta-analysis. Odds ratios (ORs) were estimated by contrasting the ratio of counts of the ‘high risk’ versus ‘low risk’ alleles in cases with dependence versus controls. Studies were analyzed by random-effects meta-analysis using pooled OR. Eleven full text articles met our eligibility criteria and nine meta-analyses were performed on three polymorphisms of CNR1: rs1049353, rs806379 and the AAT repeat. Of these, only the AAT polymorphism showed a significant association with illicit substance dependence but only in the Caucasian population samples and using a risk allele definition of ≥ 16 repeats. Our analysis showed a small effect size (OR = 1.55, P = 0.045), with strong heterogeneity (Q = 19.87, P < 0.01 with I2 = 85%). In line with the polygenic model, our meta-analysis supports a minor implication for CNR1 AAT polymorphism in illicit substance dependence vulnerability. Further studies in well-phenotyped samples and using more polymorphisms are needed to conclude on the actual influence of cannabinoid receptor polymorphisms.

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