Evaluating the relationship between Ex3 vNTR and rs3758653 polymorphisms in DRD4 genes in children with attention deficit hyperactivity disorder with respect to the dose of methylphenidate

Background. Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders starting at an early age with symptoms of attention deficit hyperactivity disorder and impulsivity. This study aimed to investigate the molecular alterations of the DRD4 gene, which have been linked to ADHD in previous studies with respect to the dose of methylphenidate.

Methods. The study population included all ADHD patients needing drug therapy aged 5-18 years referred to Bozorgmehr psychiatric clinic in Tabriz in 2017 for one year. After diagnosis, symptoms severity was assessed using the Conners Scale for ADHD Assessment. Then, 4 ml of blood was collected from each individual and DNA was extracted using salting out method. After performing polymerase chain reaction (PCR), the products were separated using specific restriction enzymes and then polymorphisms of Ex3 VNTR and rs3758653 of DRD4 gene were analyzed in 2% agarose gel. The last dose to achieve the therapeutic response was recorded in mg/kg. Then, we investigated the relationship between the doses of drug used to achieve the therapeutic response and the existence of the mentioned polymorphisms.

Results. There was no significant relationship between treatment response and type of polymorphism. Also, there was no significant relationship between the average dose of drug and the polymorphisms of three replicates, four replicates, six replicates, and more than six replicates in EX3VNTR in DRD4 gene. In addition, we witnessed no statistically significant relationship between the mean drug dose and CC, TC, and TT genotypes in DRD4rs3758653.

Conclusion. There was no significant relationship between treatment response and type of polymorphism. There was no significant relationship between the average dose of drug and the polymorphisms of three replicate, four replicates, six replicates and more than six replicates in EX3VNTR in DRD4 gene. Between mean drug dose and CC, TC and TT genotypes in DRD4rs3758653, there was no statistically significant relationship.

Practical Implications. Determining the reduction of ADHD symptoms by taking methylphenidate and evaluating the relationship between presence or absence of DRD4 polymorphisms and the dosage of drug to achieve a better response to treatment can collect enough evidence to determine the dose of methylphenidate according to the molecular analysis of DRD4 gene in patients with ADHD. This can reduce doctor visits, save time, and decrease the drug side effects.