Nonsynonymous HTR2C polymorphism predicts cortisol response to psychosocial stress II: Evidence from two samples.
Nonsynonymous HTR2C polymorphism predicts cortisol response to psychosocial stress II: Evidence from two samples.
复制标题
非同义 HTR2C 多态性预测皮质醇对心理社会压力的反应 II：来自两个样本的证据。
DOI：
10.1016/j.psyneuen.2016.04.022
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发表时间：
2016
影响因子：
3.7
通讯作者：
Taylor,ShelleyE
中科院分区：
文献类型：
--
作者：
Way,BaldwinM;Brown,KirkWarren;Quaglia,Jordan;McCain,Nancy;Taylor,ShelleyE
5-HT2C受体是位于下丘脑促肾上腺皮质激素释放激素(CRH)神经元中的主要5-羟色胺受体。这些神经元启动信号级联，最终导致皮质醇的释放。因此，5-HT2C受体基因(HTR2C)的遗传变异是影响皮质醇应激反应的主要因素。因此，我们在两个在不同地点进行的Trier社会压力测试中，研究了HTR2C非同义多态(Cys23Ser；rs6318)与应激反应的相关性。在研究1(N=1128)和研究2(N=1185)中，Cys23纯合子女性和半合子男性的皮质醇反应性更强。这种多态与自我报告的情感反应(研究1和研究2)或心血管反应性(研究2)没有关系。此外，在研究1和研究2(先前报道)中，5-羟色胺转运体基因的短/短基因多态(5-HTTLPR)与更高的皮质醇反应性相关。在这两项研究中，Cys23Ser多态和5-HTTLPR与皮质醇反应性独立相关。这些发现强调了5-羟色胺系统中的遗传变异在调节皮质醇对社会评价压力的反应性方面的重要作用。将目前的关联与先前研究的关联进行比较，强调了情景和心理因素在决定基因和表型之间关联的方向和大小方面可能的重要性。
The 5-HT2Creceptor is the primary serotonin receptor located in the corticotrophin releasing hormone (CRH) neurons of the hypothalamus. These neurons initiate the signaling cascade that culminates in cortisol release. Therefore, genetic variation in the 5-HT2Creceptor gene (HTR2C) is a prime candidate for affecting cortisol reactivity to stress. Accordingly, we examined the association of a nonsynonymous polymorphism (Cys23Ser; rs6318) inHTR2Cwith stress reactivity in two Trier Social Stress Tests conducted at separate sites. In both Study 1 (N= 128) and Study 2 (N= 185), Cys23 homozygous females and hemizygous males had greater cortisol reactivity. There was no relation between this polymorphism and self-reported affective response (Studies 1 and 2) or cardiovascular reactivity (Study 2). Additionally, the short/short genotype of a polymorphism (5-HTTLPR) in the serotonin transporter gene was associated with greater cortisol reactivity in Study 1 as well as in Study 2 (previously reported). The Cys23Ser polymorphism and the 5-HTTLPR were independently associated with cortisol reactivity in both studies. These findings emphasize the important role of genetic variation in the serotonin system on regulating cortisol reactivity to social evaluative stress. Comparison of the present associations with those of prior studies underscores the likely importance of situational and psychological factors in determining the direction and magnitude of the association between genotype and phenotype.