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

Pharmacogenomics J. 2007 Dec;7(6):368-79. doi: 10.1038/sj.tpj.6500430. Epub 2007 Jan 2.

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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • 5' Flanking Region
  • Alcoholism / enzymology
  • Alcoholism / genetics*
  • Antisocial Personality Disorder / enzymology
  • Antisocial Personality Disorder / genetics*
  • Case-Control Studies
  • DNA Mutational Analysis
  • Exons
  • Finland
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Lod Score
  • Male
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Receptor, trkB / genetics*
  • Risk Factors
  • White People / genetics*

Substances

  • Receptor, trkB