Genetic variation in dopamine pathways differentially associated with smoking progression in adolescence.
OBJECTIVE
To clarify the nature of the association between dopamine genes and smoking by examining whether genetic variability in components of the dopamine pathway could explain refined phenotypes in adolescent smoking progression.


METHODS
Data are from an ongoing prospective study of the long-term outcome of early risk factors studied since birth. At age 15 years, 220 participants (108 males, 112 females) completed a self-report questionnaire measuring smoking behavior and were genotyped for five dopamine gene variants.


RESULTS
Smoking initiation was related to allelic variation in the dopamine D4 receptor gene (DRD4), whereas smoking continuation and dependence showed association with the dopamine D2 receptor gene (DRD2). Adolescents with the seven-repeat allele of the common DRD4 exon 3 polymorphism had rates of ever smoking that were significantly higher than in those with other genotypes. Once smoking started, carriers of the T allele of a single nucleotide polymorphism of DRD2 (rs4648317) reported higher rates of current smoking and scored higher on nicotine dependence than their allelic counterparts. Among current smokers, intention to quit was significantly lower in adolescents homozygous for the 10-repeat allele of the common dopamine transporter 3' untranslated region polymorphism.


CONCLUSIONS
Our results provide preliminary evidence of genetic influences on different stages of smoking and suggest the importance of specific dopamine genes in smoking progression in adolescence.
Laucht
Manfred
M
Drs. Laucht, Becker, Schmidt, and Skowronek, Mr. Frank, and Mr. Treutlein are with the Central Institute of Mental Health; Dr. Esser is with the Department of Psychology, University of Potsdam; and Dr. Schumann is with the Institute of Psychiatry, King's College London.. Electronic address: manfred.laucht@zi-mannheim.de.
Becker
Katja
K
Drs. Laucht, Becker, Schmidt, and Skowronek, Mr. Frank, and Mr. Treutlein are with the Central Institute of Mental Health; Dr. Esser is with the Department of Psychology, University of Potsdam; and Dr. Schumann is with the Institute of Psychiatry, King's College London.
Frank
Josef
J
Drs. Laucht, Becker, Schmidt, and Skowronek, Mr. Frank, and Mr. Treutlein are with the Central Institute of Mental Health; Dr. Esser is with the Department of Psychology, University of Potsdam; and Dr. Schumann is with the Institute of Psychiatry, King's College London.
Schmidt
Martin H
MH
Drs. Laucht, Becker, Schmidt, and Skowronek, Mr. Frank, and Mr. Treutlein are with the Central Institute of Mental Health; Dr. Esser is with the Department of Psychology, University of Potsdam; and Dr. Schumann is with the Institute of Psychiatry, King's College London.
Esser
Günter
G
Drs. Laucht, Becker, Schmidt, and Skowronek, Mr. Frank, and Mr. Treutlein are with the Central Institute of Mental Health; Dr. Esser is with the Department of Psychology, University of Potsdam; and Dr. Schumann is with the Institute of Psychiatry, King's College London.
Treutlein
Jens
J
Drs. Laucht, Becker, Schmidt, and Skowronek, Mr. Frank, and Mr. Treutlein are with the Central Institute of Mental Health; Dr. Esser is with the Department of Psychology, University of Potsdam; and Dr. Schumann is with the Institute of Psychiatry, King's College London.
Skowronek
Markus H
MH
Drs. Laucht, Becker, Schmidt, and Skowronek, Mr. Frank, and Mr. Treutlein are with the Central Institute of Mental Health; Dr. Esser is with the Department of Psychology, University of Potsdam; and Dr. Schumann is with the Institute of Psychiatry, King's College London.
Schumann
Gunter
G
Drs. Laucht, Becker, Schmidt, and Skowronek, Mr. Frank, and Mr. Treutlein are with the Central Institute of Mental Health; Dr. Esser is with the Department of Psychology, University of Potsdam; and Dr. Schumann is with the Institute of Psychiatry, King's College London.
D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D000483:Alleles; D001921:Brain / Q000503:physiopathology; D018450:Disease Progression; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D014644:Genetic Variation / Q000235:genetics*; D005858:Germany; D006720:Homozygote; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D012307:Risk Factors; D012907:Smoking / Q000235:genetics* / Q000503:physiopathology; D016540:Smoking Cessation / Q000523:psychology; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000503:physiopathology
D020413:3' Untranslated Regions; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4