title: Association of THR105Ile, a functional polymorphism of histamine N-methyltransferase (HNMT), with alcoholism in German Caucasians.
abstract: 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.
authors.affiliation: Department of Psychology, Otto-Behaghel-Str. 10F, Justus-Liebig-University of Giessen, D-35394 Giessen, Germany. martin.reuter@psychol.uni-giessen.de
authors.forename: Martin
authors.initials: M
authors.lastname: Reuter
authors.forename: Neelum
authors.initials: N
authors.lastname: Jeste
authors.forename: Thomas
authors.initials: T
authors.lastname: Klein
authors.forename: Juergen
authors.initials: J
authors.lastname: Hennig
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Mary-Anne
authors.initials: MA
authors.lastname: Enoch
authors.forename: Gabor
authors.initials: G
authors.lastname: Oroszi
mesh_terms: 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
chemical_list: D017931:DNA Primers; D007532:Isoleucine; D013912:Threonine; D006637:Histamine N-Methyltransferase