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. 2008 Jan;33(2):353-60.
doi: 10.1038/sj.npp.1301406. Epub 2007 Apr 4.

Molecular genetics of the platelet serotonin system in first-degree relatives of patients with autism

Sarah Cross  1 , Soo-Jeong Kim, Lauren A Weiss, Ryan J Delahanty, James S Sutcliffe, Bennett L Leventhal, Edwin H Cook Jr, Jeremy Veenstra-Vanderweele
Affiliations

Molecular genetics of the platelet serotonin system in first-degree relatives of patients with autism

Sarah Cross et al. Neuropsychopharmacology. 2008 Jan.

Abstract

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.

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Figures

Figure 1
Figure 1. Altered Km and Vmax by SLC6A4 diplotype group
Mean values with standard error of the mean of [14C]-5-HT binding affinity Km (A) and [14C]-5-HT uptake Vmax (B) are shown for each of three SLC6A4 diplotype groups. Subjects in the TT/TT group had two haplotypes (i.e., a diplotype) containing the SNP10-SNP11 T-T haplotype. All of these subjects had HTTLPR S/S or S/L genotypes. Subjects in the L/L group had two haplotypes containing the HTTLPR L allele. Subjects in the ‘Other’ group had other combinations of haplotypes and all had HTTLPR S/S or S/L genotypes.
Figure 2
Figure 2. Altered whole blood 5-HT by TPH1 diplotype group
Mean values with standard error of the mean of whole blood 5-HT are shown for subjects with three different TPH1 diplotypes, containing either none, one, or two copies of the rs1799913-rs623580 haplotype.
See this image and copyright information in PMC

References

    1. Abramson RK, Wright HH, Carpenter R, Brennan W, Lumpuy O, Cole E, Young SR. Elevated blood serotonin in autistic probands and their first-degree relatives. Journal of Autism and Developmental Disorders. 1989;19:397–407. - PubMed
    1. Anderson GM, Feibel FC, Cohen DJ. Determination of serotonin in whole blood, platelet-rich plasma, platelet-poor plasma and plasma ultrafiltrate. Life Sci. 1987;40:1063–1070. - PubMed
    1. Anderson GM, Gutknecht L, Cohen DJ, Brailly-Tabard S, Cohen JH, Ferrari P, et al. Serotonin transporter promoter variants in autism: functional effects and relationship to platelet hyperserotonemia. Mol Psychiatry. 2002;7:831–836. - PubMed
    1. Anderson GM, Young JG, Cohen DJ, Schlicht KR. Liquid-chromatographic determination of serotonin and tryptophan in whole blood and plasma. Clinical Chemistry. 1981;27:775–776. - PubMed
    1. Arora R, Meltzer H. A modified assay for determining serotonin uptake in human platelets. Clinical Chemistry Acta. 1981;112:225–233. - PubMed

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