Gene for the serotonin transporter and ADHD: No association with two functional polymorphisms

Evidence from both human and animal studies implicates the serotonergic system in the development of attention-deficit hyperactivity disorder (ADHD) including positive association studies for several key serotonergic genes. The serotonin transporter (HTT) regulates the availability of serotonin by reuptake of the neurotransmitter from the synaptic cleft. Several studies have reported an association of this gene to ADHD, specifically the long variant of a common insertion/deletion polymorphism located in the promoter of this gene that results in increased transcription and higher HTT expression. An additional study found no evidence for an association with this polymorphism. Recently, an A/G single nucleotide polymorphism (SNP) was found within the promoter polymorphism with functional studies indicating that the long variant containing the G allele at this site behaves like the short variant. This previously unidentified functional change may have confounded earlier association studies. We investigated the relationship of several variants to ADHD: the promoter polymorphisms, SNP in the 3' untranslated region (3'UTR) with a reported association to ADHD and a rare, non-synonymous coding SNP. These polymorphisms were genotyped in 209 ADHD families identified through an affected proband. We did not find evidence for an association of these polymorphisms, or haplotypes of these polymorphisms, to ADHD in this sample. (c) 2006 Wiley-Liss, Inc.