Elevated platelet
serotonin (5-hydroxytryptamine, 5-HT) is found in a subset of children with
autism and in some of their first-degree relatives. Indices of the platelet
serotonin system, including whole blood
5-HT,
5-HT binding affinity for the
serotonin transporter (K(m)),
5-HT uptake (V(max)), and
lysergic acid diethylamide (
LSD) receptor binding, were previously studied in 24 first-degree relatives of probands with
autism, half of whom were selected for elevated whole blood
5-HT levels. All subjects were then genotyped for selected polymorphisms at the SLC6A4, HTR7, HTR2A, ITGB3, and TPH1 loci. Previous studies allowed an a priori prediction of SLC6A4 haplotypes that separated the subjects into three groups that showed significantly different
5-HT binding affinity (K(m), p=0.005) and
5-HT uptake rate (V(max), p=0.046). Genotypes at four individual polymorphisms in SLC6A4 were not associated with platelet
5-HT indices. Haplotypes at SLC6A4 and individual genotypes of polymorphisms at SLC6A4, HTR7, HTR2A, ITGB3, and TPH1 showed no significant association with whole blood
5-HT. Haplotype analysis of two polymorphisms in TPH1 revealed a nominally significant association with whole blood
5-HT (p=0.046). These initial studies of indices of the
5-HT system with several single-nucleotide polymorphisms at loci in this system generate hypotheses for testing in other samples.