Department of Biological Sciences, College of Science & Technology, Dankook University, Cheonan, South Korea.
Department of Biological Sciences, College of Science & Technology, Dankook University, Cheonan, South Korea.
Behav Brain Res. 2021 Sep 24;414:113508. doi: 10.1016/j.bbr.2021.113508. Epub 2021 Aug 3.
Attention deficit hyperactivity disorder (ADHD) is a common and heritable childhood psychiatric disorder. Recently, many studies reported a down-regulated hypothalamus-pituitary-adrenal axis (HPA-axis) with low cortisol levels in children with ADHD. The FK506 binding protein 5 or FKBP5 gene regulates the negative feedback of the HPA-axis, and genetic variants in this gene showed an association with ADHD. We investigated the genetic association between FKBP5 gene polymorphisms and susceptibility to ADHD in Korean children. We conducted a case-control study with 150 ADHD children and 322 controls. Genotyping of FKBP5 rs9394309 and rs7748266 was performed by using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). Our results showed that rs7748266 polymorphism has significant genotype (p = 0.021) and allele (p = 0.009) frequency differences between children with ADHD and the control group. CT genotype [odds ratio (OR) 1.70, 95 % confidence interval (CI) 1.134-2.540, p = 0.010] and T allele (OR 1.54, 95 % CI 1.114-2.117, p = 0.009) were associated with increased risk of ADHD. In addition, dominant (p = 0.006) and over-dominant genetic (p = 0.016) models showed significant associations with ADHD. In the stratified analysis, a significant result was obtained from the girl samples (p = 0.048). The OR of the girls with ADHD with CT genotype was 2.29 (95 % CI 1.170-4.469, p = 0.014). In contrast to rs7748266 polymorphism, rs9394309 polymorphism did not show any significant result (p > 0.05). Haplotype analysis also revealed a significant difference of the TG haplotype for rs7748266 - rs9394309 (p = 0.028, global haplotype association p-value of 0.0091). Conclusively, we confirmed that FKBP5 gene polymorphisms were associated with ADHD in Korean children. These results suggested that FKBP5 may factor in the development of ADHD.
注意缺陷多动障碍（ADHD）是一种常见的遗传性儿童期精神疾病。最近，许多研究报告称，ADHD 儿童的下丘脑-垂体-肾上腺轴（HPA 轴）功能降低，皮质醇水平降低。FK506 结合蛋白 5 或 FKBP5 基因调节 HPA 轴的负反馈，该基因的遗传变异与 ADHD 有关。我们研究了 FKBP5 基因多态性与韩国儿童 ADHD 易感性的遗传相关性。我们进行了一项病例对照研究，共纳入 150 名 ADHD 儿童和 322 名对照。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对 FKBP5 rs9394309 和 rs7748266 进行基因分型。我们的结果表明，rs7748266 多态性在 ADHD 患儿和对照组之间存在显著的基因型（p=0.021）和等位基因（p=0.009）频率差异。CT 基因型（比值比[OR]1.70，95%置信区间[CI]1.134-2.540，p=0.010）和 T 等位基因（OR 1.54，95%CI 1.114-2.117，p=0.009）与 ADHD 风险增加相关。此外，显性（p=0.006）和超显性遗传模型（p=0.016）与 ADHD 也存在显著关联。在分层分析中，来自女孩样本的结果具有显著意义（p=0.048）。携带 CT 基因型的 ADHD 女孩的 OR 为 2.29（95%CI 1.170-4.469，p=0.014）。与 rs7748266 多态性不同，rs9394309 多态性没有显示出任何显著结果（p>0.05）。单体型分析也显示 rs7748266-rs9394309 上 TG 单体型存在显著差异（p=0.028，全局单体型关联 p 值为 0.0091）。综上所述，我们证实 FKBP5 基因多态性与韩国儿童 ADHD 有关。这些结果表明 FKBP5 可能是 ADHD 发病的一个因素。
