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Open Access 01-04-2019 | Psychiatry and Preclinical Psychiatric Studies - Original Article

Association study and a systematic meta-analysis of the VNTR polymorphism in the 3′-UTR of dopamine transporter gene and attention-deficit hyperactivity disorder

Authors: Edna Grünblatt, Anna Maria Werling, Alexander Roth, Marcel Romanos, Susanne Walitza

Published in: Journal of Neural Transmission | Issue 4/2019

Abstract

Attention-deficit hyperactivity disorder (ADHD) has been postulated to associate with dopaminergic dysfunction, including the dopamine transporter (DAT1). Several meta-analyses showed small but significant association between the 10-repeat allele in the DAT1 gene in 3′-untranslated region variant number tandem repeat polymorphism and child and adolescent ADHD, whereas in adult ADHD the 9-repeat allele was suggested to confer as risk allele. Interestingly, recent evidence indicated that the long-allele variants (10 repeats and longer) might confer to lower expression of the transporter in comparison to the short-allele. Therefore, we assessed here the association in samples consisting of families with child and adolescent ADHD as well as a case–control sample, using either the 10- versus 9-repeat or the long- versus short-allele approach. Following, we conducted a systematic review and meta-analysis, including family and case–control studies, using the two aforementioned approaches as well as stratifying to age and ethnicity. The first approach (10-repeat) resulted in nominal significant association in child and adolescent ADHD (OR 1.1050 p = 0.0128), that became significant stratifying to European population (OR 1.1301 p = 0.0085). The second approach (long-allele) resulted in significant association with the whole ADHD population (OR 1.1046 p = 0.0048), followed by significant association for child and adolescent ADHD (OR 1.1602 p = 0.0006) and in Caucasian and in European child and adolescent ADHD (OR 1.1310 p = 0.0114; OR 1.1661 p = 0.0061; respectively). We were not able to confirm the association reported in adults using both approaches. In conclusion, we found further indication for a possible DAT1 gene involvement; however, further studies should be conducted with stringent phenotyping to reduce heterogeneity, a limitation observed in most included studies.

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Title: Association study and a systematic meta-analysis of the VNTR polymorphism in the 3′-UTR of dopamine transporter gene and attention-deficit hyperactivity disorder
Authors: Edna Grünblatt
Anna Maria Werling
Alexander Roth
Marcel Romanos
Susanne Walitza
Publication date: 01-04-2019
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 4/2019
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-019-01998-x

Keynote webinar | Spotlight on medication adherence

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Association study and a systematic meta-analysis of the VNTR polymorphism in the 3′-UTR of dopamine transporter gene and attention-deficit hyperactivity disorder

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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