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α-2a肾上腺素能受体基因G等位基因纯合性与韩国注意缺陷多动障碍儿童及青少年对哌甲酯反应之间的关联。

Association between homozygosity of a G allele of the alpha-2a-adrenergic receptor gene and methylphenidate response in Korean children and adolescents with attention-deficit/hyperactivity disorder.

作者信息

Cheon Keun-Ah, Cho Dae-Yeon, Koo Min-Seong, Song Dong-Ho, Namkoong Kee

机构信息

Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea.

出版信息

Biol Psychiatry. 2009 Apr 1;65(7):564-70. doi: 10.1016/j.biopsych.2008.12.003. Epub 2009 Jan 15.

Abstract

BACKGROUND

Methylphenidate (MPH) blocks the norepinephrine transporter as well as the dopamine transporter. The alpha-2a-adrenergic receptor is a key component of the noradrenergic system. The aim of this study was to evaluate the association between the ADRA2A -1291 C>G polymorphism and the response to MPH treatment in Korean subjects with attention-deficit/hyperactivity disorder (ADHD).

METHODS

This study enrolled 114 ADHD children (mean age = 9.08 +/- 1.94 years) from a child psychiatric clinic in South Korea. Subjects who had an improvement of >/= 50% compared with the baseline ADHD rating scale (ARS) score or who had a Clinical Global Impression-improvement score of 1 or 2 points after treatment were defined as the "good response". We examined the relationship of the ADRA2A to MPH response.

RESULTS

We found that a good response to MPH treatment, measured by the ARS as assessed by the parents, was observed for 76.9% of the subjects carrying the G/G genotype but for only 46.0% and 41.7% of those with the C/G and C/C genotypes, respectively [chi(2)(2) = 11.929, p = .003]. We also found a significant difference in the change in total ARS scores between subjects with and without the G/G genotype [t(1) = 2.21, p = .029].

CONCLUSIONS

Our findings provide evidence of an association between the ADRA2A -1291 C>G genotype and response to MPH treatment in Korean subjects with ADHD. Nonetheless, the methodological limitation of not being a randomized placebo-controlled trial and primarily basing results on parent report to clinicians suggest that these results should be viewed as more preliminary.

摘要

背景

哌甲酯(MPH)可阻断去甲肾上腺素转运体以及多巴胺转运体。α-2a-肾上腺素能受体是去甲肾上腺素能系统的关键组成部分。本研究旨在评估韩国注意缺陷/多动障碍(ADHD)患者中ADRA2A -1291 C>G多态性与MPH治疗反应之间的关联。

方法

本研究纳入了韩国一家儿童精神科诊所的114名ADHD儿童(平均年龄 = 9.08 ± 1.94岁)。与基线ADHD评定量表(ARS)评分相比改善≥50%或治疗后临床总体印象改善评分为1或2分的受试者被定义为“良好反应者”。我们研究了ADRA2A与MPH反应之间的关系。

结果

我们发现,携带G/G基因型的受试者中,76.9%对MPH治疗有良好反应(以父母评估的ARS衡量),而携带C/G和C/C基因型的受试者中,这一比例分别仅为46.0%和41.7%[χ(2)(2) = 11.929,p = .003]。我们还发现,有和没有G/G基因型的受试者之间,ARS总分变化存在显著差异[t(1) = 2.21,p = .029]。

结论

我们的研究结果提供了证据,表明韩国ADHD患者中ADRA2A -1291 C>G基因型与MPH治疗反应之间存在关联。尽管如此,由于本研究并非随机安慰剂对照试验,且主要基于家长向临床医生的报告得出结果,这些方法学上的局限性表明这些结果应被视为更具初步性。

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