Polymorphisms in the FKBP5 gene are associated with attention deficit and hyperactivity disorder in Korean children

Abstract

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. 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\u2009=\u2009 0.006) and over-dominant genetic (p\u2009=\u2009 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\u2009>\u2009 0.05). Haplotype analysis also revealed a significant difference of the TG haplotype for rs7748266 - rs9394309 (p\u2009=\u2009 0.028, global haplotype association p-value of 0.0091). Conclusively, we confirmed that FKBP5 polymorphisms were associated with ADHD in Korean children. These results suggested that FKBP5 may factor in the development of ADHD.