Lee Ji-Yeon, Hwang In-Wook, Lim Myung-Ho, Kwon Ho-Jang, Jin Han-Jun
Department of Nanobiomedical Science, Dankook University, Cheonan 330-714, Republic of Korea.
Environmental Health Center, Dankook Medical Hospital, Cheonan, Republic of Korea; Department of Psychology, College of Public Welfare, Dankook University, Cheonan, Republic of Korea.
Gene. 2016 Jul 25;586(2):228-33. doi: 10.1016/j.gene.2016.04.010. Epub 2016 Apr 6.
Attention deficit and hyperactivity disorder (ADHD) is highly heritable disorder and common in school-age children characterized by inattention, hyperactivity and impulsivity. Although its heritability was estimated at 80-90% from family, adoption and twin studies, the molecular etiology of this disorder has not elucidated. Meanwhile, an impaired balance of oxidant-antioxidant status and increased oxidative stress is observed in ADHD, and it may imply a possible relationship between oxidative stress and etiology of ADHD. Glutathione S-transferase (GST) is antioxidant enzymes that play a key role in the cellular detoxification. In the present study, we examined the association between the genetic polymorphisms of GSTM1, GSTP1 and GSTT1, and ADHD in Korean children. Case-control study was conducted with 243 ADHD children and 327 controls. There were no significant associations between the polymorphisms and the incidence of ADHD (p>0.05). However, significant associations were observed in the stratified analyses. The frequency of GSTP1 Ile/Ile genotype is reached to the significant level in the hyperactivity subtype (88.2%) compared to controls (64.8%) (p=0.035) and the frequency of GSTT1-null genotype is significantly higher in the inattentive boys (p=0.005). Similarly, GSTT1-null genotype showed significant associations in combined subtype (p=0.016) and hyperactivity subtype (p=0.036) of the ADHD girls. Thus our result imply that the polymorphisms in the GST genes may affect ADHD, however, replication study for larger sample set and functional studies are crucial to confirm these findings.
注意缺陷多动障碍(ADHD)是一种遗传性很高的疾病,在学龄儿童中很常见,其特征为注意力不集中、多动和冲动。尽管通过家族、收养和双胞胎研究估计其遗传度为80%-90%,但该疾病的分子病因尚未阐明。同时,在ADHD患者中观察到氧化-抗氧化状态失衡以及氧化应激增加,这可能意味着氧化应激与ADHD病因之间存在潜在关系。谷胱甘肽S-转移酶(GST)是在细胞解毒中起关键作用的抗氧化酶。在本研究中,我们检测了韩国儿童中GSTM1、GSTP1和GSTT1基因多态性与ADHD之间的关联。对243例ADHD儿童和327例对照进行了病例对照研究。基因多态性与ADHD发病率之间无显著关联(p>0.05)。然而,在分层分析中观察到了显著关联。与对照组(64.8%)相比,多动亚型中GSTP1 Ile/Ile基因型的频率达到显著水平(88.2%)(p=0.035),在注意力不集中的男孩中GSTT1缺失基因型的频率显著更高(p=0.005)。同样,GSTT1缺失基因型在ADHD女孩的组合亚型(p=0.016)和多动亚型(p=0.036)中也显示出显著关联。因此,我们的结果表明GST基因多态性可能影响ADHD,然而,对更大样本集的重复研究和功能研究对于证实这些发现至关重要。