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
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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