Lack of association between the dopamine D2 receptor gene allele DRD2*A1 and cigarette smoking in a United Kingdom population

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The dopamine D2 receptor gene contains a TaqI repeat fragment length polymorphism creating two alleles DRD2*A1 and DRD2*A2. It has been previously suggested that the lesser allele, DRD2*A1, is more prevalent in individuals who are susceptible to impulsive/addictive/compulsive behaviour, for example, alcoholics, polysubstance abusers and tobacco smokers. We genotyped a series of 104 smokers and 117 non smokers and compared the allele frequencies between the groups. A subset (n = 87) of the smoking population also completed the Classification of Smoking by Motives questionnaire and were given scores for five criteria that drive smoking: automatic, dependence, sedative, stimulant and indulgence. Another subset (n = 52) completed the Fagerstrom Tolerance Questionnaire and were given scores for nicotine dependence. We did not find any increase in allele A1 frequency when comparing smokers to non smokers. Furthermore, neither measure of dependence was affected by possession of the A1 allele; the only difference between DRD2*A1 bearing and DRD2*A2 homozygous individuals in terms of smoking motives was found in the scores for indulgence; the former having a moderately reduced score (by 17%, p < 0.05). We conclude that, in the individuals studied, the dopamine D2 receptor TaqI locus does not affect the drive to smoke. This may be caused by the locus being unrelated to impulsive/addictive/compulsive behaviour, the polymorphism being in linkage disequilibrium with another distinct locus or, alternatively, smoking may represent a behaviour that is not directly comparable to impulsive/addictive/compulsive behaviours previously associated with the DRD2*A1 allele.

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