title: Association of SNAP-25, SLC6A2, and LPHN3 with OROS methylphenidate treatment response in attention-deficit/hyperactivity disorder.
abstract: OBJECTIVE
  Our study aimed to identify the association of norepinephrine transporter gene (SLC6A2), synaptosomal-associated protein of the 25-kDa gene (SNAP-25), and latrophilin 3 gene (LPHN3) with osmotic-controlled release oral delivery system methylphenidate (OROS MPH) treatment response.
  
  
  METHODS
  One hundred thirty-nine children and adolescents with attention-deficit/hyperactivity disorder (ADHD) were recruited. We selected rs192303, rs3785143 in SLC6A2; rs3746544 (1065 T>G) in SNAP-25; and rs6551665, rs1947274, and rs2345039 in LPHN3 to examine the association of OROS MPH treatment response with each single nucleotide polymorphism. We first defined good response group when the Korean version of the ADHD rating scale score at 8 weeks was decreased for more than 50% of baseline scores and compared genotype frequencies in good response group with poor group. Second, we defined it when the Clinical Global Impression-Improvement score at 8 weeks was 1 or 2, and we also analyzed the genotype frequencies.
  
  
  RESULTS
  There was a significant association between the 1065 T>G of SNAP-25 gene and OROS MPH response, with the good response group defined by the Korean version of ADHD rating scale scores; 33.3% of the subjects with GG genotype showed a good response, whereas 74.7% of those with TT genotype and 72.5% of those with TG genotype showed good responses (P=0.034). SLC6A2 rs192303 was related with OROS MPH treatment response when we defined good treatment response by Clinical Global Impression-Improvement (P=0.009).
  
  
  CONCLUSIONS
  Our study suggested that SNAP-25 gene and SLC6A2 were involved with OROS MPH response.
authors.affiliation: *Department of Psychiatry, National Health Insurance Service, Ilsan Hospital, Goyang; †Suicide and School Mental Health Research Center, Anyang; ‡Department of Clinical pharmacology, Busan Paik Hospital, Busan; §Department of Neuropsychiatry, College of Medicine, Hallym University, Anyang; ║Department of Pharmacology, Pharmacogenomic Research Center for Membrane Transporters, Brain Korea 21 PLUS Project for Medical Science, College of Medicine, Yonsei University, Seoul; and ¶Department of Psychiatry, Bundang CHA Medical Center, School of Medicine, CHA University, Seongnam, Republic of Korea.
authors.forename: Jungeun
authors.initials: J
authors.lastname: Song
authors.forename: So Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Hong
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.forename: Byoung Wook
authors.initials: BW
authors.lastname: Lee
authors.forename: Tai Kiu
authors.initials: TK
authors.lastname: Choi
authors.forename: Sang-Hyuk
authors.initials: SH
authors.lastname: Lee
authors.forename: Ki-Hwan
authors.initials: KH
authors.lastname: Yook
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D044466:Asian People / Q000235:genetics; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D002648:Child; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000627:therapeutic use*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D018000:Receptors, Peptide / Q000235:genetics*; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C513284:ADGRL3 protein, human; D000697:Central Nervous System Stimulants; D050484:Norepinephrine Plasma Membrane Transport Proteins; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D050825:Synaptosomal-Associated Protein 25; D008774:Methylphenidate