SNAP-25、SLC6A2和LPHN3与注意缺陷多动障碍中奥氮平治疗反应的关联
Association of SNAP-25, SLC6A2, and LPHN3 with OROS methylphenidate treatment response in attention-deficit/hyperactivity disorder.
作者信息
Song Jungeun, Kim So Won, Hong Hyun Ju, Lee Min Goo, Lee Byoung Wook, Choi Tai Kiu, Lee Sang-Hyuk, Yook Ki-Hwan
机构信息
*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.
出版信息
Clin Neuropharmacol. 2014 Sep-Oct;37(5):136-41. doi: 10.1097/WNF.0000000000000045.
OBJECTIVES
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.
目的
我们的研究旨在确定去甲肾上腺素转运体基因（SLC6A2）、25 kDa突触体相关蛋白基因（SNAP-25）和促离子型受体3基因（LPHN3）与渗透控释口服给药系统哌甲酯（OROS MPH）治疗反应之间的关联。
方法
招募了139名患有注意力缺陷多动障碍（ADHD）的儿童和青少年。我们在SLC6A2中选择了rs192303、rs3785143；在SNAP-25中选择了rs3746544（1065 T>G）；在LPHN3中选择了rs6551665、rs1947274和rs2345039，以研究OROS MPH治疗反应与每个单核苷酸多态性之间的关联。我们首先将8周时韩国版ADHD评定量表评分降低超过基线评分50%的组定义为良好反应组，并比较良好反应组与不良反应组的基因型频率。其次，当8周时临床总体印象改善评分为1或2时进行定义，我们还分析了基因型频率。
结果
SNAP-25基因的1065 T>G与OROS MPH反应之间存在显著关联，以韩国版ADHD评定量表评分定义良好反应组；GG基因型的受试者中有33.3%表现出良好反应，而TT基因型的受试者中有74.7%以及TG基因型的受试者中有72.5%表现出良好反应（P=0.034）。当我们以临床总体印象改善来定义良好治疗反应时，SLC6A2 rs192303与OROS MPH治疗反应相关（P=0.009）。
结论
我们的研究表明，SNAP-25基因和SLC6A2与OROS MPH反应有关。
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