Association of dopamine, serotonin, and nicotinic gene polymorphisms with methylphenidate response in ADHD

Gene polymorphisms of the 3' untranslated region (3'-UTR) of the dopamine transporter (DAT1), Dopamine receptor exon 3 D4 variable number tandem repeat (DRD4VNTR), nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) and serotonin transporter promoter (SLC6A4-5HTTLPR) are under consideration as potential risk factors for attention-deficit/hyperactivity disorder (ADHD). A post-hoc attempt was made to investigate the association between the allelic variations of these candidate genes and retrospective parental report of response to methylphenidate in an ADHD-enriched, population-based twin sample. Subjects (N = 243) were selected from the twin sample based on parent report that the child had been treated with methylphenidate for ADHD symptoms. The functional polymorphisms screened were the VNTR located in the 3'-UTR of the dopamine transporter, DRD4 VNTR, CHRNA4 (rs1044396 and rs6090384) and the long (L(A) and L(G)) and short (S) forms of the serotonin transporter promoter region. Logistic regression did not demonstrate a significant association between methylphenidate treatment response and the relevant polymorphisms. The sample size had high power to detect effect sizes similar to those reported in some prior methylphenidate pharmacogenetic studies; however, the categorical (yes/no) measure of parent-reported treatment response may not have been sensitive enough to pick up statistically significant differences in treatment response based on genotype. Further studies including quantitative measures of treatment response are warranted.