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与注意力缺陷多动障碍相关的应激反应基因:一项针对中国儿童的病例对照研究

Stress response genes associated with attention deficit hyperactivity disorder: A case-control study in Chinese children.

作者信息

Chen Xinzhen, Wang Min, Zhang Qi, Hou Yuwei, Huang Xin, Li Shanyawen, Wu Jing

机构信息

Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Behav Brain Res. 2019 May 2;363:126-134. doi: 10.1016/j.bbr.2019.01.051. Epub 2019 Jan 29.

DOI:10.1016/j.bbr.2019.01.051
PMID:30707907
Abstract

To explore the associations between stress response genes and attention deficit hyperactivity disorder (ADHD) in children, we conducted a case-control study consisting of 406 newly diagnosed ADHD cases and 432 controls in Wuhan, China. We genotyped the candidate genes, nuclear receptor subfamily 3 group C member 1(NR3C1) and solute carrier family 6 member 4(SLC6A4), using the Sequenom MassARRAY technology. After correction by Bonferroni (α' = 0.05/6 = 0.008), the rs6191 SNP was found to be associated with a reduced risk of ADHD in the dominant model (OR = 0.564, 95% CI = 0.389-0.819, P = 0.003) while the rs25531 SNP was associated with an increased risk of ADHD in the multiplicative model (OR = 1.380, 95% CI = 1.111-1.714, P = 0.004). Additionally, both the rs6191 and rs25531 SNPs were significantly associated with the attention deficit factor (P = 0.006, P = 0.003, respectively) but not with the hyperactivity/impulsivity factor in the Swanson, Nolan and Pelham-IV Questionnaire (SNAP-IV) scale. Furthermore, we found that these two SNPs were significantly associated with pure ADHD, and not affected by the comorbidities (P =  0.001, P =  0.007, respectively). Besides, there was an interaction between these two SNPs. This study demonstrated the role of NR3C1 and SLC6A4 polymorphisms in ADHD, yet independent replication of the findings of this study in multi-center and multi-stage studies with large samples is warranted in the future.

摘要

为了探究应激反应基因与中国武汉儿童注意力缺陷多动障碍(ADHD)之间的关联,我们开展了一项病例对照研究,该研究包含406例新诊断的ADHD病例和432例对照。我们使用Sequenom MassARRAY技术对候选基因核受体亚家族3 C组成员1(NR3C1)和溶质载体家族6成员4(SLC6A4)进行基因分型。经Bonferroni校正(α' = 0.05/6 = 0.008)后,发现rs6191单核苷酸多态性(SNP)在显性模型中与ADHD风险降低相关(比值比[OR] = 0.564,95%置信区间[CI] = 0.389 - 0.819,P = 0.003),而rs25531 SNP在相乘模型中与ADHD风险增加相关(OR = 1.380,95% CI = 1.111 - 1.714, P = 0.004)。此外,rs6191和rs25531 SNPs均与注意力缺陷因子显著相关(分别为P = 0.006,P = 0.003),但在斯旺森、诺兰和佩勒姆第四版问卷(SNAP-IV)量表中与多动/冲动因子无关。此外,我们发现这两个SNP与单纯ADHD显著相关,且不受共病影响(分别为P = 0.001,P = 0.007)。此外,这两个SNP之间存在相互作用。本研究证明了NR3C1和SLC6A4基因多态性在ADHD中的作用,但未来有必要在多中心、多阶段的大样本研究中对本研究结果进行独立重复验证。

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