期刊
NEUROPSYCHOPHARMACOLOGY
卷 33, 期 2, 页码 353-360出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.npp.1301406
关键词
autism; serotonin; binding; platelet; genetic; association
资金
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [T35DK062719] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [T32MH065215, K20MH001065, K02MH001389] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS049261] Funding Source: NIH RePORTER
- NIDDK NIH HHS [T35 DK62719, T35 DK062719] Funding Source: Medline
- NIMH NIH HHS [K20 MH01065, T32 MH065215-06, K02 MH01389, T32 MH065215] Funding Source: Medline
- NINDS NIH HHS [R01 NS049261, NS049261] Funding Source: Medline
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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