A case-control association study of serotonin 1A receptor gene and tryptophan hydroxylase 2 gene in attention deficit hyperactivity disorder

Serotonergic system-related genes are likely to be involved in mechanisms underlying attention deficit hyperactivity disorder (ADHD). We investigated the association of serotonin the 1A receptor C-1019G single nucleotide polymorphism (HTR1A C-1019G SNP) and tryptophan hydroxylase 2 gene ―703G/T (TPH2 ― 703G/T) SNP with ADHD. All of the ADHD subjects completed a comprehensive and standardized diagnostic and psychological evaluation battery including the parents' Korean version of the ADHD Rating Scale-IV (ARS). The genotype and allele frequencies of 78 ADHD patients and 107 normal controls were analyzed for 5-HTR1A C-1019G and TPH2 ―703G/T. There were statistically significant differences in the genotype distributions and allele frequencies of HTR1A C-1019G between the ADHD group and the control group. The homozygous allele C frequency was significantly higher in ADHD patients than in controls. However, no differences in either genotype distribution or in allele frequencies of TPH2 ―703G/T were observed between the ADHD patients and the controls. In the ADHD patients, ANCOVA revealed that there were no significant differences in the subscales and total score between the ADHD probands with the CC genotype and those with the CG and GG genotypes in ARS and the Continuous Performance Test (CPT) when adjusting for age and gender. The odds ratio comparing the CC genotype group with the CG genotype group and the C allele with G was 2.12 and 1.79 respectively. Therefore, genotype CC was associated with higher risk of ADHD. Our results suggest that the HTR1A C-1079G SNP may affect susceptibility to ADHD. Further investigation with a larger number of subjects is needed in order to confirm this finding.