Molecular genetics of the platelet serotonin system in first-degree relatives of patients with autism
Molecular genetics of the platelet serotonin system in first-degree relatives of patients with autism
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DOI：
10.1038/sj.npp.1301406
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发表时间：
2008-01-01
影响因子：
7.6
通讯作者：
Veenstra-VanderWeele, Jeremy
中科院分区：
文献类型：
--
作者：
Cross, Sarah;Kim, Soo-Jeong;Veenstra-VanderWeele, Jeremy
自闭症儿童及其一级亲属中发现血小板5-羟色胺(5-羟色胺，5-羟色胺)升高。先前对24名自闭症先证者的一级亲属的血小板5-羟色胺系统指标进行了研究，包括全血5-羟色胺与5-羟色胺转运体的结合亲和力(K-m)、5-羟色胺摄取(V-max)和麦角酸二乙胺(LSD)受体结合，其中一半被选为全血5-羟色胺水平升高的患者。然后对所有受试者进行SLC6A4、HTR7、HTR2A、ITGB3和TPH1基因座的基因分型。以前的研究允许对SLC6A4单倍型进行先验预测，将受试者分为三组，显示出显著不同的5-羟色胺结合亲和力(K-m，p=0.005)和5-羟色胺摄取率(V-max，p=0.046)。SLC6A4基因4个单核苷酸多态与血小板5-羟色胺指数无关联。SLC6A4的单倍型和SLC6A4、HTR7、HTR2A、ITGB3和TPH1的个体基因多态性与全血5-羟色胺无显著关联。对TPH1两个多态的单倍型分析显示，名义上与全血5-羟色胺显著相关(p=0.046)。这些关于5-羟色胺系统指数的初步研究在该系统中的几个基因座上存在单核苷酸多态，为在其他样本中进行测试提供了假设。
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.