title: Lack of association of a functional catechol-O-methyltransferase gene polymorphism with risk of tobacco smoking: results from a multicenter case-control study.
abstract: BACKGROUND
  The catechol-O-methyltransferase (COMT) modulates dopaminergic neurotransmission in the prefrontal cortex as well as in the mesolimbic reward system. Since the reward system mediates addictive behavior, the COMT gene is a strong candidate gene regarding the pathophysiology of tobacco dependence and smoking behavior. Because of rather conflicting results in previous studies, the purpose of the present study was to test for association between a functional genetic variant in the COMT gene (single nucleotide polymorphism [SNP] rs4680) and tobacco smoking behavior.
  
  
  METHODS
  In a population-based case-control multicenter study designed for tobacco addiction research, a total of 551 current smokers of European ancestry and 548 age-matched healthy volunteers (never-smokers) were genotyped for SNP rs4680 and extensively characterized concerning their smoking behavior.
  
  
  RESULTS
  We found no association between smoking status and SNP rs4680 genotype nor did we find a significant association to the degree of tobacco dependence.
  
  
  CONCLUSIONS
  Although prefrontal cortical and ventral striatal activity are highly relevant for addictive behavior, and under partial control of COMT rs4680 genotype, no association between COMT and smoking behavior was observed. Other genetic variants may account for the high heritability of behavioral smoking phenotypes.
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany. jochen.mutschler@puk.zh.ch
authors.forename: Jochen
authors.initials: J
authors.lastname: Mutschler
authors.forename: Elvira
authors.initials: E
authors.lastname: Abbruzzese
authors.forename: Christoph
authors.initials: C
authors.lastname: von der Goltz
authors.forename: Christina
authors.initials: C
authors.lastname: Dinter
authors.forename: Arian
authors.initials: A
authors.lastname: Mobascher
authors.forename: Holger
authors.initials: H
authors.lastname: Thiele
authors.forename: Amalia
authors.initials: A
authors.lastname: Diaz-Lacava
authors.forename: Norbert
authors.initials: N
authors.lastname: Dahmen
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
authors.forename: Tomislav
authors.initials: T
authors.lastname: Majic
authors.forename: Nadine
authors.initials: N
authors.lastname: Petrovsky
authors.forename: Norbert
authors.initials: N
authors.lastname: Thuerauf
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.forename: Lena
authors.initials: L
authors.lastname: Rademacher
authors.forename: Juergen
authors.initials: J
authors.lastname: Brinkmeyer
authors.forename: Thomas
authors.initials: T
authors.lastname: Wienker
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
authors.forename: Georg
authors.initials: G
authors.lastname: Winterer
authors.forename: Falk
authors.initials: F
authors.lastname: Kiefer
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005858:Germany; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics; D044465:White People
chemical_list: D002394:Catechol O-Methyltransferase