Association of adult attention deficit hyperactivity disorder with dopamine transporter gene, dopamine D3 receptor, and dopamine D4 receptor gene polymorphisms

Abstract

Objective: Attention deficit hyperactivity disorder (ADHD) is a developmental disorder which is characterized by inattention, impulsiveness, and hyperactivity. The etiology of ADHD is not completely understood, but it is well known that the disorder has a moderate to high genetic component, with an estimated heritability of 76%. Polymorphic variants in several genes involved in regulation of the dopamine and related neurotransmitter pathways have been reported to be associated with ADHD. In this research we aimed to investigate the relationship between adult ADHD and DAT1 (dopamine transporter), DRD4 (dopamine D4 receptor), DRD3 (dopamine D3 receptor) gene polymorphisms. Method: Our study comprised unrelated 79 subjects who met DSM-IV criteria for adult ADHD and 75 controls and all were living in Denizli. All of the patients were evaluated with Wender-Utah Rating Scale and Adult ADD/ADHD DSM IV-Based Diagnostic Screening and Rating Scale. With written informed consent, a blood sample was drawn from each subject individual. Venous blood samples were collected in ethylene diamine tetra acetic acid (EDTA) containing tubes. DNA was extracted from whole blood and genetic analyses were performed as described in the literature by using Polymerase Chain Reaction method. SSPSS 15.0 for Windows was used for statistical analyses. Results: Twenty-three of ADHD patients were defined as predominantly inattentive type, 22 of ADHD patients were defined as predominantly hyperactive-impulsive, and the rest of them were defined as combined type ADHD. 10/10 and 9/10 repeats were most relevant genotypes in both study and control group for DAT1 VNTR (variable number of tandem repeat) polymorphism. 4/4 and 4/7 repeats were mostly found in both study and control groups for DRD4 7- repeat allele gene polymorphism. Ser/Ser polymorphism was the most relevant genotype in both study and control group for DRD3 Ser9Gly gene polymorphism. DAT1 VNTR, DRD3 Ser9Gly, and DRD4 7- repeat allele gene polymorphisms were not associated with ADHD. These gene polymorphisms were also not associated with subtypes of ADHD. Conclusions: We couldn't detect any association between DAT1 VNTR, DRD3 Ser9Gly, and DRD4 7- repeat allele gene polymorphisms and adult ADHD. Ethnicity and sample size are important factors at case control type genetic studies. European studies mostly reported an association between polymorphism of these genes and ADHD, but majority of Middle Eastern and Asian studies didn't report such an association between these genes and ADHD. Multi centered future studies using genome wide scan and variable tandem repeat techniques with larger samples would be helpful for understanding the role of dopaminergic system at ADHD genetics.