Serotonin (5-HT) receptor 5A sequence variants affect human plasma triglyceride levels.
Serotonin (5-HT) receptor 5A sequence variants affect human plasma triglyceride levels.
复制标题
血清素 (5-HT) 受体 5A 序列变异会影响人血浆甘油三酯水平。
DOI：
10.1152/physiolgenomics.00038.2010
复制
发表时间：
2010
影响因子：
4.6
通讯作者：
Olivier,M
中科院分区：
文献类型：
--
作者：
Zhang,Y;Smith,EM;Baye,TM;Eckert,JV;Abraham,LJ;Moses,EK;Kissebah,AH;Martin,LJ;Olivier,M
血清素（5-羟色胺，5-HT）等神经递质与瘦素和胰岛素密切合作，微调代谢和神经内分泌对饮食摄入的反应。失去对过量食物摄入的敏感性会导致肥胖、糖尿病和多种行为障碍。目前尚不清楚不同的血清素受体亚型如何响应和整合代谢信号，以及这些受体基因中的哪些遗传变异导致代谢紊乱易感性的个体差异。在北欧血统的肥胖家族中 (n= 2,209)，血清素 5A 型受体基因 HTR5A 被确定为影响血浆甘油三酯 (TG) 水平的一个重要因素，这得到了我们使用 28 个公开可用的和 12 个新发现的单核苷酸多态性 (SNP) 进行的全基因组连锁和靶向关联分析的数据的支持，其中 3 个与血浆 TG 水平密切相关 (P< 0.00125）。贝叶斯数量性状核苷酸 (BQTN) 分析确定了一个推定的因果启动子 SNP (rs3734967)，具有显着的后验概率 (P= 0.59)。通过电泳迁移率变动分析 (EMSA) 对 rs3734967 进行的功能分析显示，该 SNP 的两个等位基因与神经胶质瘤细胞系的核蛋白具有不同的结合模式。总之，HTR5A 的序列变异与北欧人群中高血浆 TG 水平密切相关，这表明血清素受体系统在人类中具有新的作用。这表明血浆 TG 水平的潜在大脑特异性调节可能是通过改变 HTR5A 的表达来实现的。
Neurotransmitters such as serotonin (5-hydroxytryptamine, 5-HT) work closely with leptin and insulin to fine-tune the metabolic and neuroendocrine responses to dietary intake. Losing the sensitivity to excess food intake can lead to obesity, diabetes, and a multitude of behavioral disorders. It is largely unclear how different serotonin receptor subtypes respond to and integrate metabolic signals and which genetic variations in these receptor genes lead to individual differences in susceptibility to metabolic disorders. In an obese cohort of families of Northern European descent (n= 2,209), the serotonin type 5A receptor gene,HTR5A, was identified as a prominent factor affecting plasma levels of triglycerides (TG), supported by our data from both genome-wide linkage and targeted association analyses using 28 publicly available and 12 newly discovered single nucleotide polymorphisms (SNPs), of which 3 were strongly associated with plasma TG levels (P< 0.00125). Bayesian quantitative trait nucleotide (BQTN) analysis identified a putative causal promoter SNP (rs3734967) with substantial posterior probability (P= 0.59). Functional analysis of rs3734967 by electrophoretic mobility shift assay (EMSA) showed distinct binding patterns of the two alleles of this SNP with nuclear proteins from glioma cell lines. In conclusion, sequence variants inHTR5Aare strongly associated with high plasma levels of TG in a Northern European population, suggesting a novel role of the serotonin receptor system in humans. This suggests a potential brain-specific regulation of plasma TG levels, possibly by alteration of the expression ofHTR5A.