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  • Clinical Implications
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Clinical Implication

Attention-deficit/hyperactivity disorder: current aspects on pharmacogenetics

The Pharmacogenomics Journal volume 3, pages 11–13 (2003)Cite this article

Attention-deficit/hyperactivity disorder (ADHD) is a very common and heterogeneous psychiatric disorder of childhood with marked inattentive, hyperactive and impulsive symptoms. In school-age children, the prevalence of ADHD is between 3 and 6%, and its symptoms persist in more than 60% of patients in adolescence and adulthood.1,2

Family, twin and adoption studies strongly support a role for genetic components in the etiology of the disorder. These studies showed both an increased risk of ADHD in the relatives of probands and a moderate to high heritability. The mode of transmission is unclear, but it is likely to be due to many genes, each of them with a small effect.3 Based on the dopaminergic theories of ADHD, dopamine genes have been the initial candidates for molecular studies. The dopamine D4 receptor gene (DRD4) and the dopamine transporter gene (DAT1) were the most studied. In both genes, the main polymorphisms investigated in association studies with ADHD are the variable number of tandem repeats (VNTR). In the DRD4 gene, this VNTR is a 48 bp sequence in the third exon that can be repeated 2–11 times. This 48 bp polymorphism shows considerable ethnic variability, but 2-, 4- and 7-repeat alleles are the most common variants across different populations. Several studies that focused on DRD4 gene found an association of the 7-repeat allele with ADHD.4 The VNTR at DAT1 gene is a 40 bp sequence in the 3′ untranslated region. In all, 10 different alleles can be found, according to the presence of 3–13 copies of the 40 bp unit. The 10-repeat allele, the most prevalent variant worldwide, has been implicated as the risk allele for ADHD.4 Two recent meta-analyses support a small effect of both genes in the disorder (Waldman et al, unpublished).5

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Acknowledgements

Contract grant sponsors: Programa de Apoio a Núcleos de Excelência (PRONEX), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Financiadora de Estudos e Projetos (FINEP), Fundação de Amparo a Pesquisa do Rio Grande do Sul (FAPERGS), FIPE (Hospital de Clínicas de Porto Alegre) and NOVARTIS Pharmaceuticals.

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Authors and Affiliations

  1. Child and Adolescent Psychiatric Division, ADHD Outpatient Clinic, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Brazil

    L A Rohde & T Roman

  2. Department of Genetics, Federal University of Rio Grande do Sul, Brazil

    T Roman & M H Hutz

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  1. L A Rohde
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  2. T Roman
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  3. M H Hutz
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Correspondence to L A Rohde.

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Rohde, L., Roman, T. & Hutz, M. Attention-deficit/hyperactivity disorder: current aspects on pharmacogenetics. Pharmacogenomics J 3, 11–13 (2003). https://doi.org/10.1038/sj.tpj.6500158

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