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Monday, February 5, 2007

Association of the neuronal nicotinic receptor 2 subunit gene (CHRNB2) with subjective responses to alcohol and nicotine

Research Article
Association of the neuronal nicotinic receptor 2 subunit gene (CHRNB2) with subjective responses to alcohol and nicotine


Marissa A. Ehringer 1 2 *, Hilary V. Clegg 1, Allan C. Collins 1 3, Robin P. Corley 1, Thomas Crowley 4, John K. Hewitt 1 3, Christian J. Hopfer 4, Kenneth Krauter 5, Jeffrey Lessem 1, Soo Hyun Rhee 1 3, Isabel Schlaepfer 1 2, Andrew Smolen 1, Michael C. Stallings 1 3, Susan E. Young 1, Joanna S. Zeiger 1

1Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado2Department of Integrative Physiology, University of Colorado, Boulder, Colorado3Department of Psychology, University of Colorado, Boulder, Colorado4Department of Psychiatry, Division of Substance Dependence, University of Colorado School of Medicine, Denver, Colorado5Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado

email: Marissa A. Ehringer (Marissa.Ehringer@colorado.edu)

*Correspondence to Marissa A. Ehringer, University of Colorado, Institute for Behavioral Genetics 447 UCB, Boulder, CO 80309.

Abstract
Nicotine addiction and alcohol dependence are highly comorbid disorders that are likely to share overlapping genetic components.

We have examined two neuronal nicotinic receptor subunit genes (CHRNA4 and CHRNB2) for possible associations with nicotine and alcohol phenotypes, including measures of frequency of use and measures of initial subjective response in the period shortly after first using the drugs.

The subjects were 1,068 ethnically diverse young adults participating in ongoing longitudinal studies of adolescent drug behaviors at the University of Colorado, representing both clinical and community samples.

Analysis of six SNPs in the CHRNA4 gene provided modest support for an association with past 6 month use of alcohol in Caucasians (three SNPs with P < 0.08), but no evidence for an association with tobacco and CHRNA4 was detected.

However, a SNP (rs2072658) located immediately upstream of CHRNB2 was associated with the initial subjective response to both alcohol and tobacco.

This study provides the first evidence for association between the CHRNB2 gene and nicotine- and alcohol-related phenotypes, and suggests that polymorphisms in CHRNB2 may be important in mediating early responses to nicotine and alcohol
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