DAT1 and DRD4 genes involved in key dimensions of adult ADHD

Article Article scientifique Article DAT1 and DRD4 genes involved in key dimensions of adult ADHD eng 2015 author Hasler Roland 510492 author Salzmann Annick 0000-0003-0571-251X 510521 author Bolzan Tiffany 672191 author Zimmermann Julien 512866 author Baud Patrick 26940 author Giannakopoulos Panteleimon 44657 author Perroud Nader Ali 0000-0002-9282-9216 94458 861-869 10.1007/s10072-014-2051-7 25555995 1590-1874 Attention-deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder often persisting in adulthood. Genetic studies of ADHD mainly focused on the Dopamine Transporter (DAT1) and the Dopamine Receptor 4 (DRD4) genes. Nevertheless, polymorphisms of these genes explain only a small fraction of the assigned risk, suggesting that intermediate dimensions and environmental factors should also be considered. We investigated in 77 adult ADHD subjects compared to 474 controls, how polymorphisms within the genes coding for DAT1 (40-bp VNTR in 3'UTR), the Dopamine Receptor 2 (DRD2) (rs1799732) and DRD4 (48-bp VNTR in exon 3), may modulate the expression of the disorder. By genotyping DAT1, we detected a new 9.5R allele showing a deletion of 40 bp and also an insertion of 19 bp compared to the 10R allele. This novel allele was found to be significantly protective for ADHD (p < 0.0001). Another significant difference was found in the distribution of DRD4 48-bp VNTR 6R allele when comparing patients and controls (p = 0.0007). In addition significant results were also found for DAT1 9.5R allele, which was associated with impulsiveness (p = 1.98 × 10(-4)) and trait anger scores (p = 7.66 × 10(-4)). Moreover, impulsiveness scores were partly modulated by an interaction between the DRD4 48-bp VNTR 6R allele and childhood maltreatment (p = 0.01), however, this result did not resist correction for multiple comparisons. Altogether, our results show the putative involvement of DAT1 and DRD4 genes in the aetiology of ADHD with a main role in modulation of key dimensions of the disorder. Dewey 616.89 60 Département de psychiatrie 225 false 161 Groupe Giannakopoulos Panteleimon (psychiatrie générale) 201 417 Thérapeutiques des Troubles de l'Humeur et Anxieux 689 Neurological sciences 36 6 3e9b2002-9db3-4796-bf60-85681c0a1fb5 Article (Published version) Restricted art%3A10.1007%2Fs10072-014-2051-7.pdf 788224 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de psychiatrie

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DAT1 and DRD4 genes involved in key dimensions of adult ADHD	Neurological sciences			2015	680	1

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Bolzan, Tiffany