Association between glycogen synthase kinase-3β gene polymorphisms and attention deficit hyperactivity disorder in Korean children: a preliminary study

Abstract

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.