Cho Soo-Churl, Kim Jae-Won, Kim Boong-Nyun, Hwang Jun-Won, Park Mira, Kim Soon Ae, Cho Dae-Yeon, Yoo Hee-Jeong, Chung Un-Sun, Son Jung-Woo, Park Tae-Won
Department of Child and Adolescent Psychiatry, College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Am J Med Genet B Neuropsychiatr Genet. 2008 Sep 5;147B(6):957-63. doi: 10.1002/ajmg.b.30725.
Previous studies have demonstrated that the MspI and DraI polymorphisms at the alpha-2A-adrenergic receptor gene (ADRA2A) are associated with ADHD. However, few studies have been designed to ascertain the association between the ADRA2A genotypes and the performance on neurocognitive measures in ADHD. The aims of this study were to examine the association of the ADRA2A MspI and DraI polymorphisms with ADHD in Korean subjects, and to determine the relationship between the genotypes of these two polymorphisms and the candidate endophenotypes, as measured by the continuous performance test (CPT). In a case-control study, we assessed 186 ADHD probands and 150 normal controls. One hundred eight trios were studied in a family based association analysis. The transmission disequilibrium test (TDT) analysis showed preferential transmission of the C allele of the DraI polymorphism (chi(2) = 5.88, P = 0.015). In the haplotype analyses, a trend of over-transmission of haplotype C/C was observed (chi(2) = 3.80, P = 0.051). The homozygous subjects for the C allele (C/C genotype) at the DraI polymorphism showed a trend toward a higher mean T-score with respect to the response time variability profiles of the CPT than did those with the other genotypes (C/T + T/T genotypes; P = 0.042). The homozygous subjects for the G allele (G/G genotype) at the MspI polymorphism showed a tendency to have a lower mean T-score with respect to the response time variability profiles of the CPT (P = 0.068). The results of this study provide important evidence for the involvement of the ADRA2A MspI and DraI polymorphisms in the etiology of ADHD in Korean subjects. In addition, our results provide evidence for the possible role of these two polymorphisms in ADHD symptom expression, such as increased response time variability.
先前的研究表明，α-2A-肾上腺素能受体基因（ADRA2A）的MspI和DraI多态性与注意力缺陷多动障碍（ADHD）有关。然而，很少有研究旨在确定ADRA2A基因分型与ADHD患者神经认知测量表现之间的关联。本研究的目的是检验韩国人群中ADRA2A的MspI和DraI多态性与ADHD的关联，并通过连续性能测试（CPT）确定这两种多态性的基因型与候选内表型之间的关系。在一项病例对照研究中，我们评估了186名ADHD先证者和150名正常对照。在一项基于家庭的关联分析中研究了108个三联体。传递不平衡检验（TDT）分析显示DraI多态性的C等位基因存在优先传递（χ2 = 5.88，P = 0.015）。在单倍型分析中，观察到C/C单倍型的过度传递趋势（χ2 = 3.80，P = 0.051）。DraI多态性的C等位基因纯合子受试者（C/C基因型）在CPT反应时间变异性方面的平均T分数往往高于其他基因型（C/T + T/T基因型）的受试者（P = 0.042）。MspI多态性的G等位基因纯合子受试者（G/G基因型）在CPT反应时间变异性方面的平均T分数往往较低（P = 0.068）。本研究结果为ADRA2A的MspI和DraI多态性参与韩国人群ADHD的病因提供了重要证据。此外，我们的结果为这两种多态性在ADHD症状表达中的可能作用提供了证据，例如反应时间变异性增加。
