Analysis of genetic variations of protein tyrosine kinase fyn and their association with alcohol dependence in two independent cohorts

Biol Psychiatry. 2003 Dec 15;54(12):1422-6. doi: 10.1016/s0006-3223(03)00635-8.

Abstract

Background: Decreased sensitivity to and increased tolerance for the effects of alcohol is a phenotype, which was shown to be associated with an increased risk for alcoholism in humans and was observed in protein tyrosine kinase (PTK) fyn knockout mice.

Methods: We performed an association study of genetic variations of PTK fyn in 430 alcohol-dependent patients and 365 unrelated control subjects from two independent samples.

Results: In a combined analysis, we found an association of alcohol dependence with the single nucleotide polymorphism (SNP) T137346C in the 5' untranslated region (UTR) of the gene. A relevant association could be excluded for the remaining two informative SNPs. Selection by phenotype showed that a high number of withdrawal symptoms, high amount of alcohol intake, and high maximum number of drinks compared with unrelated control subjects was associated with the SNP in the 5'-UTR region but not with the remaining SNPs.

Conclusions: Our results indicate a possible association of alcohol dependence with a genotype of the SNP T137346C of the PTK fyn, with C being the risk allele.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Adult
  • Alanine / genetics
  • Alcoholism / genetics*
  • Alcoholism / metabolism
  • Case-Control Studies
  • Chi-Square Distribution
  • Cohort Studies
  • Cysteine / genetics
  • Female
  • Gene Frequency
  • Genetic Variation*
  • Genotype
  • Glycine / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-fyn
  • Threonine / genetics

Substances

  • 5' Untranslated Regions
  • Proto-Oncogene Proteins
  • Threonine
  • FYN protein, human
  • Proto-Oncogene Proteins c-fyn
  • Cysteine
  • Alanine
  • Glycine