CYP450 2D6 and 2C19 genotypes in ADHD: not related with treatment resistance but with over-representation of 2C19 ultra-metabolizers

Kutuk, Meryem Ozlem and Tufan, Ali Evren and Topal, Zehra and Acikbas, Ufuk and Guler, Gulen and Karakaş, Bahriye and Başağa, Hüveyda and Kilicaslan, Fethiye and Altintas, Ebru and Aka, Yeliz and Kutuk, Ozgur (2022) CYP450 2D6 and 2C19 genotypes in ADHD: not related with treatment resistance but with over-representation of 2C19 ultra-metabolizers. Drug Metabolism and Personalized Therapy, 37 (3). pp. 261-269. ISSN 2363-8907 (Print) 2363-8915 (Online)

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Abstract

Cytochrome P450 (CYP450) is a major enzyme system involved in drug metabolism as well as regulation of brain function. Although individual variability in CYP enzymes have been studied in terms of personality traits and treatment effects, no study up to now evaluated CYP polymorphisms in children with attention deficit/hyperactivity disorder (ADHD). We aimed to define the genetic profiles of CYP2D6 and CYP2C19 relevant alleles in children with ADHD according to treatment status and compare the frequencies according to past results. Three hundred and seventeen patients with ADHD-Combined Presentation were enrolled; symptom severity was evaluated by parents and clinicians while adverse effects of previous treatments were evaluated with parent and child reports. Reverse blotting on strip assays was used for genotyping and descriptive and bivariate analyses were conducted. A p-value was set at 0.05 (two-tailed). Children were divided into treatment-naïve (n=194, 61.2%) and treatment-resistant (n=123, 38.8%) groups. Within the whole sample PM, EM and UM status according to 2D6 were 3.8% (n=12), 94.3% (n=299) and 21.9% (n=6); respectively. PM, IM, EM and UM status according to 2C19 were 2.5% (n=8), 19.8% (n=63), 48.6% (n=154) and 29.0% (n=92), respectively. No relationship with treatment resistance, comorbidity or gender could be found. Importantly, CYP2C19 UMs were significantly more frequent in ADHD patients compared to previous studies in the general population. CYPs may be a rewarding avenue of research to elucidate the etiology and treatment of patients with ADHD.
Item Type: Article
Uncontrolled Keywords: attention deficit/hyperactivity disorder; CYP2C19; CYP2D6; pharmacogenetics; therapy resistance
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Hüveyda Başağa
Date Deposited: 06 Sep 2023 14:29
Last Modified: 06 Sep 2023 14:29
URI: https://research.sabanciuniv.edu/id/eprint/47775

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