Dopamine transporter and receptor polymorphisms associated with variability in dose-response
FRIDAY, Oct. 21 (HealthDay News) -- Dopamine transporter (DAT) and dopamine receptor D4 (DRD4) polymorphisms may be correlated with dose-response variability to methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder (ADHD), according to a study published online Sept. 19 in the Journal of the American Academy of Child & Adolescent Psychiatry.
Tanya E. Froehlich, M.D., from Cincinnati Children's Hospital Medical Center, and colleagues examined the role of four catecholamine-related candidate genes in moderating MPH dose-response in 89 stimulant-naive children (aged 7 to 11 years) with ADHD. Each child's response to three MPH dosage levels was compared with the response to placebo using the Vanderbilt ADHD rating scales. Polymorphisms in the 3' untranslated region of DAT, exon 3 on DRD4, codon 158 on catechol-O-methyltransferase, and the adrenergic α2A receptor promoter were genotyped. Gene, dose, and gene-by-dose effects on inattentive and hyperactive-impulsive domain outcomes were assessed using linear mixed models.
The investigators found that the most statistically significant gene-by-dose interactions were seen on hyperactive-impulsive symptoms for DRD4 and DAT polymorphisms. On increasing the MPH dose, the ADHD symptoms improved significantly more in children lacking the DAT 10-repeat allele compared with 10-repeat carriers. Across all MPH doses, children lacking the DRD4 four-repeat allele showed less improvement compared to participants with the four-repeat allele.
"DAT and DRD4 polymorphisms may be associated with individual variability in MPH dose-response," the authors write.
Several authors disclosed financial ties to the pharmaceutical industry.
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