1. ¹Sections on Molecular Genetics and Human Genetics, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
2. ²Department of Psychiatry, University of Helsinki, Finland

Correspondence: Dr RH Lipsky, Section on Molecular Genetics, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 3S32, Rockville, MD 20852, USA. E-mail: rlipsky@mail.nih.gov

Received 31 May 2006; Revised 6 September 2006; Accepted 2 October 2006; Published online 2 January 2007.

Abstract

To identify sequence variants in genes that may have roles in neuronal responses to alcohol, we resequenced the 5' region of tyrosine kinase B neurotrophin receptor gene (NTRK2) and determined linkage disequilibrium (LD) values, haplotype structure, and performed association analyses using 43 single nucleotide polymorphisms (SNPs) covering the entire NTRK2 region in a Finnish Caucasian sample of 229 alcohol-dependent subjects with antisocial personality disorder (ASPD) and 287 healthy controls. Individually, three SNPs were associated with alcohol dependence and alcohol abuse (AD) (P-value from 0.0019 to 0.0059, significance level was set at P0.01 corrected for multiple testing), whereas a common 18 locus haplotype within the largest LD block of NTRK2, a 119-kb region containing the 5' flanking region and exons 1–15, was marginally overrepresented in control subjects compared to AD individuals (global P=0.057). Taken together, these results support a role for the NTRK2 gene in addiction in a Caucasian population with AD and a subtype of ASPD.