Carboxylesterase 1 gene polymorphism and methylphenidate response in ADHD.
Methylphenidate (MPH) is the most frequently prescribed drug in the treatment of attention deficit hyperactivity disorder (ADHD). Several pharmacogenetic studies suggested that catecholamine candidate genes influence individual MPH-responses, but these results are mostly contradictory. Genetic analyses of MPH metabolizing carboxylesterase 1 enzyme (CES1) have not been carried out, whereas, meta-analysis of CYP2D6 genetic variants has been already indicated significant pharmacogenetic differences in atomoxetine treatment. Here we present an association analysis of the CES1 Gly143Glu functional polymorphism in a Hungarian ADHD group (n = 173). The genotype frequencies were similar to that of the general population (5.8% vs 4.1% of Gly/Glu heterozygote). Pharmacogenetic analysis was conducted among 122 ADHD children treated with MPH. Neither the categorical analysis comparing 90 responders vs 32 non-responders, nor the dimensional analysis of Inattention and Hyperactivity-Impulsivity score reduction showed a significant main genotype effect. However, analyzing the daily dose, we observed an association with the rare 143Glu-variant: 5 patients in the responder group carrying the Glu-allele required lower doses of MPH for symptom reduction (0.410 +/- 0.127 vs 0.572 +/- 0.153 mg/kg, t(1,88) = 2.33, p = 0.022). This result warrants for further investigations of the CES1 gene in larger ADHD samples.
Nemoda
Zsofia
Z
Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary. zsofia.nemoda@eok.sote.hu
Angyal
Nora
N
Tarnok
Zsanett
Z
Gadoros
Julia
J
Sasvari-Szekely
Maria
M
D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000201:enzymology; D043182:Carboxylesterase / Q000235:genetics*; D002265:Carboxylic Ester Hydrolases; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D011110:Polymorphism, Genetic
D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human; D043182:Carboxylesterase