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Association of the DRD4 Exon III Polymorphism With Smoking in Fifteen-Year-Olds: A Mediating Role for Novelty Seeking?

https://doi.org/10.1097/01.chi.0000155980.01792.7fGet rights and content

ABSTRACT

Objective

This study was designed to examine the role of DNA variants of the dopamine D4 receptor gene (DRD4) in smoking experimentation in adolescents and to determine the extent to which novelty seeking (NS) could account for a possible effect of DRD4 on tobacco use.

Method

Participants were from a longitudinal study of an original birth cohort (born 1986-1988) of 384 children from a high-risk community sample. At age 15 years, adolescents completed a self-report questionnaire measuring tobacco consumption and temperament (Junior Temperament and Character Inventory). DNA was taken from 303 participants (144 males, 159 females) and genotyped for the DRD4 exon III polymorphism.

Results

DRD4 was associated with smoking status and NS in males but not in females. Males with the seven repeat allele exhibited more smoking involvement (p < .002) and scored higher in NS (p < .002) than males without this allele. In addition, elevated tobacco use was related to a higher level of NS in both males and females (p < .001). Multiple regression analyses revealed that NS mediated the relationship between DRD4 and smoking in males.

Conclusions

These findings highlight the importance of considering the mechanisms underlying the association between genetic factors and tobacco use separately by gender and, possibly, by developmental period.

Section snippets

Participants

Participants in this investigation are members of the Mannheim Study of Risk Children, an ongoing prospective longitudinal study of the long-term outcome of early risk factors followed from birth to adolescence (Laucht et al., 2000). The sample consisted of an original cohort of 384 infants born between February 1, 1986, and February 28, 1988, who were recruited from two obstetric and six children's hospitals of the Rhine-Neckar Region of Germany. To be included in the study, parents and

Demographics

Demographic and clinical characteristics for male and female adolescents in the DRD4 7r groups are presented in Table 1. Results indicated that groups did not differ significantly regarding age, IQ, family adversity, and obstetric risk score. In addition, no significant differences according to gender were observed.

Association of DRD4 With Smoking and NS

Table 2 presents measures of smoking status for male and female adolescents in the DRD4 7r groups. Compared with data from a recent survey of smoking behavior in German adolescents (

DISCUSSION

Nicotine is one of the most addictive substances known, and tobacco use that begins in adolescence can become a serious addiction with long-term health consequences. This study indicates that genetic variation in the DRD4 gene may confer a risk for greater smoking activity during the early stages of smoking in adolescents. Fifteen-year-old males carrying the 7r allele of the exon III polymorphism had higher rates of lifetime smoking and smoking consumption and tend to be younger at their

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    Disclosure: Drs. Becker and Schmidt currently receive research funding from Eli Lilly. Dr. Schmidt also receives research funding from Johnson & Johnson. The other authors have no financial relationships to disclose.

    This study was supported by grants from the Deutsche Forschungsgemeinschaft and from the Federal Ministry for Education and Research (01EB0110), Baden-Wuerttemberg Consortium for Addiction Research. The authors thank the parents and children for their participation in the study and Ruth Berg and Sabine Eichenherr for their work in the lab.

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