Interaction of Dopamine Transporter Genotype with Prenatal Smoke Exposure on ADHD Symptoms

Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany.
The Journal of pediatrics (Impact Factor: 3.79). 03/2008; 152(2):263-9. DOI: 10.1016/j.jpeds.2007.07.004
Source: PubMed


To demonstrate that children homozygous for the 10-repeat allele of the common dopamine transporter (DAT1) polymorphism who were exposed to maternal prenatal smoke exhibited significantly higher hyperactivity-impulsivity than children without these environmental or genetic risks.
We performed a prospective longitudinal study from birth into early adulthood monitoring the long-term outcome of early risk factors. Maternal prenatal smoking was determined during a standardized interview with the mother when the child was 3 months old. At age 15 years, 305 adolescents participated in genotyping for the DAT1 40 base pair variable number of tandem repeats polymorphism and assessment of inattention, hyperactivity-impulsivity, and oppositional defiant/conduct disorder symptoms with the Kiddie-Sads-Present and Lifetime Version.
There was no bivariate association between DAT1 genotype, prenatal smoke exposure and symptoms of attention deficit hyperactivity disorder. However, a significant interaction between DAT1 genotype and prenatal smoke exposure emerged (P = .012), indicating that males with prenatal smoke exposure who were homozygous for the DAT1 10r allele had higher hyperactivity-impulsivity than males from all other groups. In females, no significant main effects of DAT1 genotype or prenatal smoke exposure or interaction effects on any symptoms were evident (all P > .25).
This study provides further evidence for the multifactorial nature of attention deficit hyperactivity disorder and the importance of studying both genetic and environmental factors and their interaction.

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Available from: Günter Esser, Jan 27, 2014
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    • "Moreover, several male-specific associations between SLC6A3/ DAT1 40 bp-VNTR and behavioral phenotypes were already reported (e.g. prenatal smoke exposure and ADHD (Becker et al. 2008), number of sexual partners (Guo et al. 2007a), violent delinquency (Guo et al. 2007b) and sleep–wake cycles (Valomon et al. 2014 "
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    • "Future work should examine this idea empirically and evaluate whether males are differentially susceptible to positive environmental conditions (e.g., proper nutrition) during pregnancy in such a way as to decrease DBD risk. This type of work has important implications for the development of prevention strategies, suggesting that pregnant women, particularly those expecting boys, may especially benefit from refraining from use of alcohol and nicotine during pregnancy (Becker et al., 2008; Bennett et al., 2007). Notably, results were significant using measures that did not contain shared source variance (i.e., when utilizing teacher report of symptoms and parent report of prenatal stressor exposure), although, interestingly , results did not hold using parent-report of symptoms. "
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    • "In the most recent meta-analysis,19 significant evidence of association was found with the 480-bp allele of the most commonly studied polymorphism (a VNTR in the 3′ untranslated region (UTR) region of the gene) as well as with other polymorphisms in the same gene. The substantial heterogeneity reported could be the result of multiple polymorphisms in this gene increasing risk to ADHD or gene–environment interaction between the 3′ UTR VNTR and prenatal factors, such as maternal alcohol consumption22 or maternal smoking during pregnancy,23 although these associations have not been widely replicated. "
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