Nucleotide sequence variation within the human tyrosine kinase B neurotrophin receptor gene: association with antisocial alcohol dependence

• Published in: The pharmacogenomics journal Vol. 7; no. 6; pp. 368 - 379
• Main Authors: Xu, K, Anderson, T R, Neyer, K M, Lamparella, N, Jenkins, G, Zhou, Z, Yuan, Q, Virkkunen, M, Lipsky, R H
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.12.2007
• Subjects: 5' Flanking Region; Addictions; Alcohol; Alcohol abuse; Alcoholism - enzymology; Alcoholism - genetics; Antisocial personality disorder; Antisocial Personality Disorder - enzymology; Antisocial Personality Disorder - genetics; Case-Control Studies; DNA Mutational Analysis; Drug abuse; Drug dependence; European Continental Ancestry Group - genetics; Exons; Finland; Genetic Predisposition to Disease; Haplotypes; Humans; Linkage Disequilibrium; Lod Score; Male; Nucleotide sequence; Phenotype; Polymorphism, Single Nucleotide; Protein-tyrosine kinase; Receptor, trkB - genetics; Risk Factors; Single-nucleotide polymorphism; Social behavior; White people; Finland
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/sj.tpj.6500430

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 P<or=0.01 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.