A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans
A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans
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DOI：
10.1523/jneurosci.3769-04.2005
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发表时间：
2005-03-09
影响因子：
5.3
通讯作者：
Grasby, PM
中科院分区：
文献类型：
--
作者：
David, SP;Murthy, NV;Grasby, PM
在人类中，5-HT 1A受体与焦虑和抑郁症及其治疗有关。然而，控制5-HT 1A受体表达的生理和遗传因素在健康和疾病中是不确定的。在这项研究中，使用5-HT 1A选择性正电子发射断层扫描（PET）配体[C-11] WAY 100635评估了两种遗传因素对活体人脑中5-HT 1A受体表达的影响。在对140名健康志愿者进行基因分型以研究5-HT 1A受体基因中已知单核苷酸多态性（SNP）的群体频率后，在一组35名健康个体中用[11 C] WAY 100635扫描检查常见SNP [（-1018）C > G]对5-HT 1A受体表达的影响。在PET组中，我们还研究了5-HT转运蛋白（5-HTT）基因的常见可变数目串联重复多态性[短（S）和长（L）等位基因]对5-HT 1A受体密度的影响。然而，5-HT 1A受体基因型对[11 C] WAY 100635结合没有任何显著影响，5-HT 1A受体结合电位值在5-HTTLPR短（SS或SL）基因型受试者的所有脑区均低于长（LL）基因型受试者。虽然PET组是一个小样本量的遗传关联研究，我们的研究结果表明，第一次在5-HTT基因的功能多态性，而不是5-HT 1A受体基因，影响5-HT 1A受体在man. The结果可能提供一个合理的生理机制之间的关联5-HTTLPR基因型，行为特征和情绪状态。
In humans, 5-HT1A receptors are implicated in anxiety and depressive disorders and their treatment. However, the physiological and genetic factors controlling 5-HT1A receptor expression are undetermined in health and disease. In this study, the influence of two genetic factors on 5-HT1A receptor expression in the living human brain was assessed using the 5-HT1A-selective positron emission tomography (PET) ligand [C-11] WAY 100635. After the genotyping of 140 healthy volunteers to study population frequencies of known single nucleotide polymorphisms (SNPs) in the 5-HT1A receptor gene, the influence of the common SNP [(-1018) C > G] on 5-HT1A receptor expression was examined in a group of 35 healthy individuals scanned with [11C] WAY 100635. In the PET group, we also studied the influence of a common variable number tandem repeat polymorphism [short (S) and long (L) alleles] of the 5-HT transporter (5-HTT) gene on 5-HT1A receptor density. Whereas, the 5-HT1A receptor genotype did not show any significant effects on [11C] WAY 100635 binding, 5-HT1A receptor binding potential values were lower in all brain regions in subjects with 5-HTTLPR short (SS or SL) genotypes than those with long (LL) genotypes. Although the PET groups are necessarily a small sample size for a genetic association study, our results demonstrate for the first time that a functional polymorphism in the 5-HTT gene, but not the 5-HT1A receptor gene, affects 5-HT1A receptor availability in man. The results may offer a plausible physiological mechanism underlying the association between 5-HTTLPR genotype, behavioral traits, and mood states.