Abstract
To investigate the role of the corticotropin releasing hormone receptor 1 (CRHR1) in patterns of human alcohol drinking and its potential contribution to alcohol dependence, we analysed two independent samples: a sample of adolescents, which consisted of individuals from the ‘Mannheim Study of Risk Children’ (MARC), who had little previous exposure to alcohol, and a sample of alcohol-dependent adults, who met DSM-IV criteria of alcohol dependence. Following determination of allelic frequencies of 14 polymorphisms of the CRHR1 gene, two haplotype tagging (ht)SNPs discriminating between haplotypes with a frequency of ⩾0.7% were identified. Both samples were genotyped and systematically examined for association with the htSNPs of CRHR1. In the adolescent sample, significant group differences between genotypes were observed in binge drinking, lifetime prevalence of alcohol intake and lifetime prevalence of drunkenness. The sample of adult alcohol-dependent patients showed association of CRHR1 with high amount of drinking. This is the first time that an association of CRHR1 with specific patterns of alcohol consumption has been reported. Our findings support results from animal models, suggesting an importance of CRHR1 in integrating gene–environment effects in alcohol use disorders.
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Acknowledgements
We thank Marina Füg and Christine Hohmeyer for expert technical assistance. We also thank Simon Heath and Ivo Gut, Centre National de Génotypage, Evry and Stefan Wellek, Division of Biostatistics, Central Institute of Mental Health for helpful discussions. This work was in part supported by two BMBF Grants: FKZ 01GS0117/NGFN to RS and GS, and FKZ EB 01011300 to RS and GS (MWK-BW Projekt 12a) and the EC TARGALC QLG3-CT-2002–01048 to RS. Additionally, it was supported by grants from the Deutsche Forschungsgemeinschaft and from the Federal Ministry for Education and Research – 01EB0110 – ‘Baden-Wuerttemberg Consortium for Addiction Research’ (Project 2) to ML and by FKZ 01GR0420/NGFN to SW.
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Treutlein, J., Kissling, C., Frank, J. et al. Genetic association of the human corticotropin releasing hormone receptor 1 (CRHR1) with binge drinking and alcohol intake patterns in two independent samples. Mol Psychiatry 11, 594–602 (2006). https://doi.org/10.1038/sj.mp.4001813
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DOI: https://doi.org/10.1038/sj.mp.4001813
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