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

Sarah Cross; Soo Jeong Kim; Lauren A. Weiss; Ryan J. Delahanty; James S. Sutcliffe; Bennett L. Leventhal; Edwin H. Cook; Jeremy Veenstra-VanderWeele

doi:10.1038/sj.npp.1301406

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

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

Obstetrics, Gynecology and Women's Health - Fetal Medicine

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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.

Original language	English (US)
Pages (from-to)	353-360
Number of pages	8
Journal	Neuropsychopharmacology
Volume	33
Issue number	2
DOIs	https://doi.org/10.1038/sj.npp.1301406
State	Published - Jan 2008

Bibliographical note

Funding Information:
Kathy Hennessy, Diane Dickel, and Laura Martinolich provided expert technical assistance. Charles Glatt generously provided information about the DPDR subject heterozygous for the SLC6A4 amino-acid variant. We are especially grateful to the subjects who participated in the study. This work was supported, in part, by NIH K02 MH01389 (EHC), NIH K20 MH01065 (GLH), NIH NS049261 (JSS), NIH T35 DK62719 (SC), the Jean Young and Walden W Shaw Foundation (BLL), the Harris Foundation (BLL), the Brain Research Foundation (EHC), University of Chicago, and the American Psychiatric Institute for Research and Education Janssen Scholars in Research on Severe Mental Illness program (JV-VW).

Keywords

Association
Autism
Binding
Genetic
Platelet
Serotonin

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title = "Molecular genetics of the platelet serotonin system in first-degree relatives of patients with autism",

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 (Km), 5-HT uptake (Vmax), 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 (Km, p=0.005) and 5-HT uptake rate (Vmax, 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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note = "Funding Information: Kathy Hennessy, Diane Dickel, and Laura Martinolich provided expert technical assistance. Charles Glatt generously provided information about the DPDR subject heterozygous for the SLC6A4 amino-acid variant. We are especially grateful to the subjects who participated in the study. This work was supported, in part, by NIH K02 MH01389 (EHC), NIH K20 MH01065 (GLH), NIH NS049261 (JSS), NIH T35 DK62719 (SC), the Jean Young and Walden W Shaw Foundation (BLL), the Harris Foundation (BLL), the Brain Research Foundation (EHC), University of Chicago, and the American Psychiatric Institute for Research and Education Janssen Scholars in Research on Severe Mental Illness program (JV-VW).",

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

Abstract

Bibliographical note

Keywords

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