Analysis of genetic variations of protein tyrosine kinase fyn and their association with alcohol dependence in two independent cohorts.
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.
Schumann
Gunter
G
Department of Psychiatry, Central Institute of Mental Health, Mannheim, Germany.
Rujescu
Dan
D
Kissling
Christian
C
Soyka
Michael
M
Dahmen
Norbert
N
Preuss
Ullrich W
UW
Wieman
Stefan
S
Depner
Martin
M
Wellek
Stefan
S
Lascorz
Jesús
J
Bondy
Brigitta
B
Giegling
Ina
I
Anghelescu
Ion
I
Cowen
Michael S
MS
Poustka
Annemarie
A
Spanagel
Rainer
R
Mann
Karl
K
Henn
Fritz A
FA
Szegedi
Armin
A
D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D000409:Alanine / Q000235:genetics; D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003545:Cysteine / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D013912:Threonine / Q000235:genetics
D020121:5' Untranslated Regions; D011518:Proto-Oncogene Proteins; D013912:Threonine; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D003545:Cysteine; D000409:Alanine; D005998:Glycine