Jeong Seong Hoon, Choi Keong-Sook, Lee Kyu Young, Kim Eui-Joong, Kim Yong-Sik, Joo Eun-Jeong
aDepartment of Psychiatry, Eulji University Hospital, Eulji University School of Medicine, Daejeon bDepartment of Psychiatry, Eulji General Hospital, Eulji University School of Medicine, Seoul cDepartment of Psychiatry, Dongguk University International Hospital, Goyang-si, Korea.
Psychiatr Genet. 2015 Jun;25(3):119-26. doi: 10.1097/YPG.0000000000000086.
The dopamine transporter gene (DAT1) is an established genetic risk factor for attention deficit hyperactivity disorder (ADHD). Therefore, we hypothesized that DAT1 may also influence the manifestation of ADHD-related traits in the normal population.
A quantitative association study was carried out on 1289 healthy adults. ADHD-related traits were measured using the 25-item Wender Utah Rating Scale (WURS-25). This scale is a self-administered instrument intended to retrospectively measure features of childhood ADHD. Previous studies typically identified three component factors: (i) impulsivity, (ii) inattention, and (iii) mood instability. Our group found that these factors were associated with various diagnoses, such as bipolar disorder and major depression. Six polymorphic markers within the DAT1 gene (rs27072, rs11133767, rs429699, rs27048, rs2937639), including the 3'-untranslated region variable number of tandem repeats, were used as genetic markers.
The WURS-25 total score was not associated with any of the markers that we examined. However, the mood instability trait was associated significantly with rs2937639 in male participants (P=0.008); this result was supported by several haplotype-wise findings among the surrounding markers (P=0.00001-0.004).
Our study results suggest that DAT1 polymorphisms may modulate mood instability traits in the normal population. Considering that mood instability tends to persist through the entire course of ADHD and is highly prevalent in many diseases that are comorbid with ADHD, this trait may be a core endophenotype that defines the role of the DAT1 gene in various psychiatric conditions.
多巴胺转运体基因（DAT1）是注意缺陷多动障碍（ADHD）已确定的遗传风险因素。因此，我们推测DAT1可能也会影响正常人群中ADHD相关特质的表现。
对1289名健康成年人进行了定量关联研究。使用25项温德犹他评定量表（WURS - 25）测量ADHD相关特质。该量表是一种自我评定工具，旨在回顾性测量儿童期ADHD的特征。以往研究通常确定了三个组成因素：（i）冲动性，（ii）注意力不集中，以及（iii）情绪不稳定。我们的研究小组发现这些因素与各种诊断相关，如双相情感障碍和重度抑郁症。DAT1基因内的六个多态性标记（rs27072、rs11133767、rs429699、rs27048、rs2937639），包括3'-非翻译区可变串联重复序列，被用作遗传标记。
WURS - 25总分与我们检测的任何标记均无关联。然而，情绪不稳定特质在男性参与者中与rs2937639显著相关（P = 0.008）；这一结果得到了周围标记中几个单倍型分析结果的支持（P = 0.00001 - 0.004）。
我们的研究结果表明，DAT1基因多态性可能调节正常人群的情绪不稳定特质。鉴于情绪不稳定往往在ADHD的整个病程中持续存在，并且在许多与ADHD共病的疾病中高度普遍，该特质可能是定义DAT1基因在各种精神疾病中作用的核心内表型。
