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Further evidence for the association between a polymorphism in the promoter region of SLC6A3/DAT1 and ADHD: findings from a sample of adults

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An Erratum to this article was published on 17 October 2016

Abstract

The dopamine transporter (SLC6A3/DAT1) plays a key role in the regulation of dopaminergic neurotransmission and is the major site of action for methylphenidate, a first-line medication for attention deficit hyperactivity disorder (ADHD). Most genetic association studies with ADHD have investigated a 40-bp variable number of tandem repeats (VNTR) polymorphism in the 3′-untranslated region (UTR) of the DAT1, but these investigations have reported heterogeneous findings. The few studies focused on the 5′ region have reported promising results. Despite rs2652511 not being included, nor having any proxy SNP available in GWAS, the few candidate gene studies that analyzed it suggested an association with ADHD and schizophrenia. Here, we analyzed the −839 C/T (rs2652511) promoter variant and the 3′-UTR and intron 8 (Int8) VNTR polymorphisms in 522 adults with ADHD and 628 blood donor controls. The diagnostic procedures followed the DSM-IV criteria. A significant association was detected (P = 0.002) between the rs2652511 C-allele with ADHD. In addition, the 6-repeat allele of Int8 VNTR was associated with higher inattention scores (P = 0.034). The haplotype analysis including DAT1 3′-UTR and Int8 VNTR polymorphisms did not reveal associations with ADHD susceptibility or severity dimensions. These findings extend to adult samples previous findings from children samples on the role of the rs2652511 polymorphism in the promoter region of DAT1 as a risk factor for ADHD susceptibility.

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Acknowledgments

The research was supported by grants from ‘Conselho Nacional de Desenvolvimento Científico e Tecnológico’ (CNPq), ‘Coordenação de Aperfeiçoamento de Pessoal de Nível Superior’ (CAPES), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul’ (FAPERGS), ‘Departamento de Ciência e Tecnologia/Programa de Pesquisa para o Sistema Único de Saúde’ (DECIT/PPSUS), and ‘Programa de Apoio a Núcleos de Excelência’ (PRONEX). Dr Francine Z. Marques is supported by National Health and Medical Research Council (APP1052659) and National Heart Foundation (PF12M6785) co-shared Early Career Fellowships.

Conflict of interest

The ADHD Program received unrestricted educational and research support from the following pharmaceutical companies in the last 3 years: Abbott, Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Novartis, and Shire. Dr Belmonte-de-Abreu is on the speakers’ bureau or is a consultant for Janssen-Cilag and Bristol-Myers Squibb. Dr Rohde was on the speakers’ bureau and/or acted as consultant for Eli Lilly, Janssen-Cilag, Novartis, and Shire in the last 3 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Novartis and Janssen-Cilag in 2010 and authorship royalties from Oxford Press and ArtMed.

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Authors and Affiliations

  1. Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Caixa Postal: 15053, Porto Alegre, RS, 91501-970, Brazil

    Lucas A. de Azeredo, Diego L. Rovaris, Nina R. Mota, Evelise R. Polina & Claiton H. D. Bau

  2. School of Health Sciences, University of Ballarat, Ballarat, VIC, Australia

    Francine Z. Marques

  3. Postgraduate Program in Biotechnology, Centro Universitário Univates, Lajeado, Brazil

    Verônica Contini

  4. ADHD Outpatient Program, Adult Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Lucas A. de Azeredo, Diego L. Rovaris, Nina R. Mota, Evelise R. Polina, Verônica Contini, Eduardo S. Vitola, Luis A. Rohde, Eugenio H. Grevet & Claiton H. D. Bau

  5. Department of Psychiatry, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Paulo Belmonte-de-Abreu & Luis A. Rohde

  6. Instituto de Psiquiatria do Desenvolvimento para a Infância e Adolescência, São Paulo, Brazil

    Luis A. Rohde

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  1. Lucas A. de Azeredo
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  2. Diego L. Rovaris
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  10. Eugenio H. Grevet
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  11. Claiton H. D. Bau
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Correspondence to Claiton H. D. Bau.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s00406-016-0739-9.

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de Azeredo, L.A., Rovaris, D.L., Mota, N.R. et al. Further evidence for the association between a polymorphism in the promoter region of SLC6A3/DAT1 and ADHD: findings from a sample of adults. Eur Arch Psychiatry Clin Neurosci 264, 401–408 (2014). https://doi.org/10.1007/s00406-014-0486-8

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