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 (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.

• Authors: Sarah Cross, Soo-Jeong Kim, Lauren A Weiss, Ryan J Delahanty, James S Sutcliffe, Bennett L Leventhal, Edwin H Cook Jr, Jeremy Veenstra-Vanderweele
• Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 33 Issue 2 Pg. 353-60 (Jan 2008) ISSN: 0893-133X [Print] England
• PMID: 17406648 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• SLC6A4 protein, human
• Serotonin Plasma Membrane Transport Proteins
• Serotonin

Topics

• Adult
• Asian People (genetics)
• Autistic Disorder (blood, genetics)
• Black People (genetics)
• Blood Platelets (physiology)
• DNA Primers
• Female
• Hispanic or Latino (genetics)
• Humans
• Male
• Nuclear Family
• Platelet Count
• Polymorphism, Genetic
• Polymorphism, Single Nucleotide
• Serotonin (blood)
• Serotonin Plasma Membrane Transport Proteins (genetics)
• White People (genetics)