Division of Child & Adolescent Psychiatry, Department of Psychiatry, Soonchunhyang University Cheonan Hospital, 8 2Gil Soonchunhyang, Cheonan City, Choongnam Province 330-721, South Korea.
Prog Neuropsychopharmacol Biol Psychiatry. 2012 Oct 1;39(1):57-61. doi: 10.1016/j.pnpbp.2012.05.008. Epub 2012 May 31.
Glycogen synthase kinase (GSK)-3β plays a key role in the phosphorylation and regulation of metabolic enzymes and many transcription factors. Recent studies have suggested the involvement of GSK-3β in the pathogenesis and treatment target of DA-associated neuropsychiatric disorders, which has led to consider GSK-beta as one of the candidate genes for those disorders. GSK-3β genes are likely to be involved in mechanisms underlying attention deficit hyperactivity disorder (ADHD). We investigated the association between -1727A/T and -50T/C SNPs of GSK-3β gene with ADHD. All ADHD subjects completed a comprehensive and standardized diagnostic test and psychological evaluation battery, including the parents' Korean version of the ADHD Rating Scale-IV (ARS). The genotype and allele frequencies of 103 ADHD patients and 173 normal controls were analyzed for -1727A/T and -50T/C SNPs of GSK-3β gene. There were statistically significant differences in the genotype distributions of the -1727A/T SNP of GSK-3β gene between the ADHD group and the control group. The frequency of the genotype AT was significantly higher in the ADHD patients. Concerning the haplotype, there was a significant difference in the A-C haplotype frequency between the two samples. However, no differences in either the genotype distribution or in allele frequencies of -50C/T were observed between the two samples. In the parents version of K-ARS of all subjects, ANCOVA revealed that two subscales and the total score were significantly higher in the subjects with AT+TT genotypes than those with AA genotype after adjusting for age and gender. The odds ratio for the ADHD patients was 1.79, comparing the AT genotype group with the AA genotype group. Therefore, genotype AT is associated with a higher risk of ADHD. Our results suggest that the -1727A/T SNP of GSK-3β gene may affect susceptibility in ADHD. Further investigation with a larger number of subjects is needed to validate this finding.
糖原合成酶激酶（GSK）-3β 在代谢酶和许多转录因子的磷酸化和调节中发挥关键作用。最近的研究表明，GSK-3β 参与了与 DA 相关的神经精神疾病的发病机制和治疗靶点，这使得 GSK-β 成为这些疾病的候选基因之一。GSK-3β 基因可能与注意缺陷多动障碍（ADHD）的发病机制有关。我们研究了 GSK-3β 基因的-1727A/T 和-50T/C 单核苷酸多态性与 ADHD 的关系。所有 ADHD 患者均完成了全面和标准化的诊断测试和心理评估，包括父母的 ADHD 评定量表-IV（ARS）。分析了 103 例 ADHD 患者和 173 例正常对照者的 GSK-3β 基因-1727A/T 和-50T/C 单核苷酸多态性的基因型和等位基因频率。ADHD 组和对照组之间 GSK-3β 基因-1727A/T 单核苷酸多态性的基因型分布存在统计学差异。ADHD 患者的 AT 基因型频率明显较高。关于单倍型，两个样本之间 A-C 单倍型频率存在显著差异。然而，两个样本之间的-50C/T 基因型分布或等位基因频率没有差异。在所有受试者的 K-ARS 父母版本中，在调整年龄和性别后，ANCOVA 显示两个亚量表和总分在 AT+TT 基因型受试者中明显高于 AA 基因型受试者。与 AA 基因型组相比，ADHD 患者的比值比为 1.79。因此，AT 基因型与 ADHD 的风险增加有关。我们的结果表明，GSK-3β 基因的-1727A/T 单核苷酸多态性可能影响 ADHD 的易感性。需要进一步的研究，以验证这一发现。
