Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD

Genetic and pharmacological studies have emphasised the role of serotonin 5-hydroxytryptamine (5-HT) as a possible etiologic factor in the development of attention-deficit hyperactivity disorder (ADHD). Tryptophan hydroxylase (TPH) is a rate-limiting enzyme in the biosynthesis of serotonin from tryptophan. Originally, the TPH gene was thought to be widely expressed, but a second form of TPH, TPH2, was recently identified and the TPH2 gene was found to be solely expressed in the brain. We examined eight single nucleotide polymorphisms ( SNP) in the TPH2 gene for association with ADHD in 179 Irish nuclear families. Transmission disequilibrium test analysis revealed significant association between the T allele of marker rs1843809 with the disorder ( chi(2) = 12.2, P = 0.0006, OR = 2.36). Stratifying data by the sex of the transmitting parent showed that this association was enhanced when paternal transmission was considered ( OR = 3.7). In addition, several haplotypes ( all including the associated marker) were associated with ADHD. These preliminary findings suggest that TPH2 is a susceptibility locus for ADHD. Further confirmation, preferably from different ethnic groups, is required to firmly implicate TPH2 in the pathophysiology of ADHD.