Molecular genetics of the platelet serotonin system in first-degree relatives of patients with autism.
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.
Cross
Sarah
S
Pritzker School of Medicine, University of Chicago, Chicago, IL, USA.
Kim
Soo-Jeong
SJ
Weiss
Lauren A
LA
Delahanty
Ryan J
RJ
Sutcliffe
James S
JS
Leventhal
Bennett L
BL
Cook
Edwin H
EH
Veenstra-Vanderweele
Jeremy
J
D000328:Adult; D044466:Asian People / Q000235:genetics; D001321:Autistic Disorder / Q000097:blood / Q000235:genetics*; D044383:Black People / Q000235:genetics; D001792:Blood Platelets / Q000502:physiology*; D017931:DNA Primers; D005260:Female; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D009679:Nuclear Family; D010976:Platelet Count; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012701:Serotonin / Q000097:blood*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D044465:White People / Q000235:genetics
D017931:DNA Primers; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin