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Catechol‐ O ‐methyltransferase Val158Met polymorphism is associated with methylphenidate response in ADHD children
Author(s) -
Kereszturi Eva,
Tarnok Zsanett,
Bognar Emese,
Lakatos Krisztina,
Farkas Luca,
Gadoros Julia,
SasvariSzekely Maria,
Nemoda Zsofia
Publication year - 2008
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30704
Subject(s) - methylphenidate , catechol o methyl transferase , catechol , attention deficit hyperactivity disorder , polymorphism (computer science) , psychology , methyltransferase , clinical psychology , genetics , genotype , chemistry , biology , biochemistry , gene , methylation
Methylphenidate is the most frequently prescribed drug in the treatment of attention deficit hyperactivity disorder (ADHD) but it is not effective in every case. Therefore, identifying genetic and/or biological markers predicting drug‐response is increasingly important. Here we present a case‐control study and pharmacogenetic association analyses in ADHD investigating three dopaminergic polymorphisms. Previous studies suggested variable number of tandem repeats (VNTR) in the dopamine D4 receptor (DRD4) and the dopamine transporter (DAT1) genes as genetic risk factors for ADHD and as possible markers of methylphenidate response. Our results did not indicate substantial involvement of these two VNTRs in ADHD, however, both the case‐control and the pharmacogenetic analyses showed significant role of the high activity Val‐allele of cathecol‐ O ‐methyltransferase (COMT) Val158Met polymorphism in our ADHD population. The Val‐allele was more frequent in the ADHD group (n = 173) compared to the healthy population ( P = 0.016). The categorical analysis of 90 responders versus 32 non‐responders showed an association between the Val‐allele or Val/Val genotype and good methylphenidate response ( P = 0.009 and P = 0.034, respectively). Analyzing symptom severity as a continuous trait, significant interaction of COMT genotype and methylphenidate was found on the Hyperactivity‐Impulsivity scale ( P = 0.044). Symptom severity scores of all three genotype groups decreased following methylphenidate administration ( P < 0.001), however Val/Val homozygote children had significantly less severe symptoms than those with Met/Met genotype after treatment ( P = 0.015). This interaction might reflect the regulatory effect of COMT dominated prefrontal dopamine transmission on subcortical dopamine systems, which are the actual site of methylphenidate action. © 2008 Wiley‐Liss, Inc.