engleski

Dopamine D4 receptor exon III polymorphism in attention-deficit/hyperactivity disorder

Dopamine plays an important role in a modulation of behaviour and cognition via fronto-striato-cerebellar circuits in which dopamine receptors represent an important link in dopamine signalling. In the third exon of the dopamine D4 receptor (DRD4) gene, there is a polymorphism consisting of a variable number of tandem repeats (VNTR). It was postulated that variations of DRD4 might result in differences in second messenger coupling or signal transduction. DRD4 variants with 6 or more repeats are assumed to be associated with different psychiatric disorders such as addictive behaviour, novelty seeking and attention-deficit/hyperactivity disorder (ADHD). ADHD is a complex disorder diagnosed through the persistence of three behavioural symptoms: impulsivity, hyperactivity and/or inattention. Aim of our study was to determine the distribution of the DRD4 genotypes in children with ADHD and in healthy children in order to investigate and to clarify the role of DRD4 in the etiology of ADHD. DRD4 genotypes were determined using polymerase chain reaction (PCR) and agarose gel electrophoresis in 139 children with ADHD (according to DSM-IV criteria) and in 134 healthy, age matched, children. There was no gender difference in the DRD4 genotypes. DRD4 genotype frequencies differed significantly between healthy children and children with ADHD, and 7-repeats allele was found more frequently in ADHD children. There were no significant differences in DRD4 genotype frequencies between different types of ADHD. Children with predominantly inattentive type of ADHD had significantly higher frequency of 7-repeats allele compared to healthy children. These findings confirmed an important association between the DRD4 VNTR polymorphism and the expression of ADHD, and/or symptoms of inattention, suggesting that genetic variations in the third exon DRD4 may be, among other factors, a risk factor in the development of ADHD.

Dopamine receptor D4; attention-deficit/hyperactivity disorder; variable number of tandem repeats

nije evidentirano