Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder
Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder
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DOI：
10.1086/503850
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发表时间：
2006-05-01
影响因子：
9.8
通讯作者：
Goldman, D
中科院分区：
文献类型：
--
作者：
Hu, XZ;Lipsky, RH;Goldman, D
一种功能性血清素转运启动子多态性，HTTLPR，改变疾病的风险以及大脑的形态和功能。这里，我们展示了HTTLPR在功能上是三等位的。L-G等位基因是具有常见G替换的L等位基因，它创建了一个功能性AP2转录因子结合位点。在代表6种基因型的62个淋巴母细胞系和转染的rape衍生细胞中的表达分析显示共显性等位基因作用，S和L-G等位基因的低表达几乎相等，说明HTT表达的差异比以前认识到的要大。在169名患有强迫症（OCD）的白人中，LALA基因型的获得性大约是253名种族匹配对照的两倍。我们对175个强迫症先证者及其父母组成的三胞胎进行了重复研究。L-A等位基因是强迫症患者的两倍过度传播。HTTLPR LALA基因型对强迫症的风险有中等（1.8倍）的影响，这明确了HTT基因在强迫症中起作用的证据。
A functional serotonin transporter promoter polymorphism, HTTLPR, alters the risk of disease as well as brain morphometry and function. Here, we show that HTTLPR is functionally triallelic. The L-G allele, which is the L allele with a common G substitution, creates a functional AP2 transcription-factor binding site. Expression assays in 62 lymphoblastoid cell lines representing the six genotypes and in transfected raphe-derived cells showed co-dominant allele action and low, nearly equivalent expression for the S and L-G alleles, accounting for more variation in HTT expression than previously recognized. The gain-of-function LALA genotype was approximately twice as common in 169 whites with obsessive-compulsive disorder (OCD) than in 253 ethnically matched controls. We performed a replication study in 175 trios consisting of probands with OCD and their parents. The L-A allele was twofold overtransmitted to the patients with OCD. The HTTLPR LALA genotype exerts a moderate (1.8-fold) effect on risk of OCD, which crystallizes the evidence that the HTT gene has a role in OCD.