Association study and a systematic meta-analysis of the VNTR polymorphism in the 3′-UTR of dopamine transporter gene and attention-deficit hyperactivity disorder
Autor: | Susanne Walitza, Anna Maria Werling, Marcel Romanos, Edna Grünblatt, Alexander Roth |
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Přispěvatelé: | University of Zurich, Grünblatt, Edna |
Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Oncology Neurology Minisatellite Repeats 2738 Psychiatry and Mental Health DAT1 0302 clinical medicine 10064 Neuroscience Center Zurich Child 3' Untranslated Regions Attention-deficit hyperactivity disorder ADHD Dopamine transporter SLC6A3 Meta-analysis education.field_of_study biology Dopaminergic 10058 Department of Child and Adolescent Psychiatry Psychiatry and Mental health 2728 Neurology (clinical) 10076 Center for Integrative Human Physiology Female 2803 Biological Psychiatry medicine.medical_specialty Adolescent Population 610 Medicine & health 03 medical and health sciences Internal medicine medicine Humans Attention deficit hyperactivity disorder Genetic Predisposition to Disease Allele education Biological Psychiatry Dopamine Plasma Membrane Transport Proteins Polymorphism Genetic business.industry Three prime untranslated region Psychiatry and Preclinical Psychiatric Studies - Original Article medicine.disease 030104 developmental biology Attention Deficit Disorder with Hyperactivity 2808 Neurology biology.protein Neurology (clinical) business 030217 neurology & neurosurgery Genome-Wide Association Study |
Zdroj: | Journal of Neural Transmission Journal of Neural Transmission, 126 (4) |
ISSN: | 1435-1463 0300-9564 |
Popis: | 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. Journal of Neural Transmission, 126 (4) ISSN:1435-1463 ISSN:0300-9564 |
Databáze: | OpenAIRE |
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