title: The homozygosity for 10-repeat allele at dopamine transporter gene and dopamine transporter density in Korean children with attention deficit hyperactivity disorder: relating to treatment response to methylphenidate.
abstract: The symptoms of attention deficit hyperactivity disorder (ADHD) can be treated with methylphenidate (MPH), a potent blocker of dopamine transporter (DAT). The homozygosity of the 10-repeat allele at the DAT gene (DAT1) seems to be associated with a poor response to MPH in children with ADHD. In the present study, we investigated the association between DAT density using I-123-N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl)tropane [123I]IPT single photon emission computed tomography (SPECT)] and the homozygosity for 10-repeat allele at DAT1 and response to MPH in Korean children with ADHD. Eleven drug-naive children with ADHD were included in the study and treated with MPH for about 8 weeks. After the genotyping and SPECT were performed, we compared DAT density between ADHD children with and without the homozygosity for 10-repeat allele at DAT1 and investigated the correlation between the homozygosity for 10-repeat allele and response to MPH. ADHD children with 10/10 genotype (n=7) had a significantly greater increase of the DAT density in basal ganglia than the children without 10/10 genotype (n=4). We found that while only 28.6% (2/7) of the subject with 10/10 genotype showed good response to MPH treatment, 100% (4/4) of the subjects without 10/10 genotype showed good response to MPH treatment. Our findings support an association between homozygosity for 10-repeat allele at DAT1 and the DAT density assessed in vivo and correlation between the homozygosity for 10-repeat allele and poor response to MPH.
authors.affiliation: Department of Psychiatry, College of Medicine, Kwandong University, Myong-Ji Hospital, 697-24 Hwajung-Dong, Dukyang-ku 412-270, Koyang, Kyunggi-Do, Republic of Korea. kacheon@dreamwiz.com
authors.forename: Keun-Ah
authors.initials: KA
authors.lastname: Cheon
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Ryu
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Dae-Yeon
authors.initials: DY
authors.lastname: Cho
mesh_terms: D000483:Alleles; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D001931:Brain Mapping; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D003710:Demography; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D007839:Functional Laterality; D006720:Homozygote; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008774:Methylphenidate / Q000627:therapeutic use*; D018598:Minisatellite Repeats / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018709:Statistics, Nonparametric; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D016896:Treatment Outcome; D014326:Tropanes
chemical_list: D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; C493214:SLC6A3 protein, human; D014326:Tropanes; C087210:N-(3-iodopropen-1-yl)-2-carbomethoxy-3-(4-chlorophenyl)tropane; D008774:Methylphenidate