Association of THR105Ile, a functional polymorphism of histamine N-methyltransferase (HNMT), with alcoholism in German Caucasians.
BACKGROUND
CNS histamine has been shown to have an inhibitory effect on reward and it is implicated in the etiology of addiction and stress. Histamine N-methyltransferase (HNMT) is believed to be the sole pathway for termination of the neurotransmitter action of histamine in mammalian brain. A common, functional polymorphism, a C314T transition in the HNMT gene, results in a Thr105Ile substitution of the protein encoded. A recent study has shown that the frequency of the Ile105 allele was significantly lower in alcoholics compared to that in non-alcoholics in Finns and Plains American Indians. Following up these results, we tested whether the Thr105Ile polymorphism was associated with alcoholism in German Caucasians.


METHODS
Thr105Ile was genotyped in n=366 psychiatrically interviewed German Caucasian ICD-10 lifetime alcoholics, along with n=200 ethnically matched controls.


RESULTS
No significant difference was found in the frequency of the Ile105 allele between alcoholics (0.11) and controls (0.10) (chi(2)=0.21, d.f.=1, p=0.647). Likewise, genotype distributions did not differ significantly. However, the frequency of the Ile105 allele was significantly lower in male alcoholics with a family history of alcoholism compared to that in male alcoholics without a family history of alcoholism (chi(2)=4.07, d.f.=1, p=0.044).


CONCLUSIONS
In German Caucasians the association of the HNMT Thr105Ile polymorphism with alcoholism was not replicated per se, but a congruent association was found between the Ile105 allele and family history of alcoholism supporting the protective role of the Ile105 allele against alcoholism.
Reuter
Martin
M
Department of Psychology, Otto-Behaghel-Str. 10F, Justus-Liebig-University of Giessen, D-35394 Giessen, Germany. martin.reuter@psychol.uni-giessen.de
Jeste
Neelum
N
Klein
Thomas
T
Hennig
Juergen
J
Goldman
David
D
Enoch
Mary-Anne
MA
Oroszi
Gabor
G
D000328:Adult; D000437:Alcoholism / Q000175:diagnosis / Q000208:ethnology* / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006637:Histamine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D038801:International Classification of Diseases; D007532:Isoleucine; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D013912:Threonine; D044465:White People / Q000235:genetics
D017931:DNA Primers; D007532:Isoleucine; D013912:Threonine; D006637:Histamine N-Methyltransferase