Hypomethylation of the Serotonin Receptor Type-2A Gene (HTR2A) at T102C Polymorphic Site in DNA Derived From the Saliva of Patients With Schizophrenia and Bipolar Disorder
Hypomethylation of the Serotonin Receptor Type-2A Gene (HTR2A) at T102C Polymorphic Site in DNA Derived From the Saliva of Patients With Schizophrenia and Bipolar Disorder
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DOI：
10.1002/ajmg.b.31192
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发表时间：
2011-07-01
影响因子：
2.8
通讯作者：
Abdolmaleky, Hamid Mostafavi
中科院分区：
文献类型：
--
作者：
Ghadirivasfi, Mohammad;Nohesara, Shabnam;Abdolmaleky, Hamid Mostafavi
若干证据线索表明，血清素信号传导和HTR2A受体功能障碍与精神分裂症（SCZ）和双相情感障碍（BD）的发病机制有关。HTR2A在T102C多态性位点的DNA甲基化影响HTR2A的表达，并且在精神分裂症和双相情感障碍患者的死后大脑中报告了HTR2A启动子的异常DNA甲基化。我们假设大脑中HTR2A的表观遗传学改变也可能存在于可作为诊断/治疗生物标志物的外周组织中，因此我们分析了从精神分裂症和双相情感障碍患者及其一级亲属以及正常对照的唾液中提取的DNA的HTR2A启动子DNA甲基化情况。亚硫酸氢盐测序用于筛选HTR2A启动子CpG岛的DNA甲基化状态，定量甲基化特异性PCR（qMSP）用于量化差异甲基化位点的胞嘧啶甲基化程度。HTR2A启动子的大多数胞嘧啶未甲基化。然而， -1438A/G多态性位点、 -1420和 -1223的CpG岛甲基化程度>95%。T102C多态性位点的CpG岛以及相邻的CpG岛在患者和对照中甲基化程度均约为70%。qMSP分析显示，与对照相比，精神分裂症、双相情感障碍及其一级亲属中T102C多态性位点的胞嘧啶显著低甲基化。来自唾液的DNA中HTR2A在T102C多态性位点的胞嘧啶甲基化有可能作为精神分裂症和双相情感障碍的诊断、预后和/或治疗生物标志物。然而，这些初步观察结果需要在更大样本量的其他人群中进行重复验证，才能考虑用于临床应用。（C）2011威利 - 利斯公司
Several lines of evidence indicate that dysfunction of serotonin signaling and HTR2A receptor are involved in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BD). DNA methylation of HTR2A at T102C polymorphic site influences HTR2A expression and aberrant DNA methylation of HTR2A promoter was reported in postmortem brain of patients with SCZ and BD. Hypothesizing that the brain's epigenetic alteration of HTR2A may also exist in peripheral tissues that can be used as a diagnostic/therapeutic biomarker, we analyzed HTR2A promoter DNA methylation in DNA extracted from the saliva of patients with SCZ and BD, and their first degree relatives versus normal controls. Bisulfite sequencing was used to screen DNA methylation status of the HTR2A promoter CpGs and qMSP was used to quantify the degree of cytosine methylation at differentially methylated sites. Most of the cytosines of the HTR2A promoter were unmethylated. However, CpGs of the -1438A/G polymorphism site, -1420 and -1223 were >95% methylated. The CpG at T102C polymorphic site and neighboring CpGs were similar to 70% methylated both in the patients and controls. qMSP analysis revealed that the cytosine of the T102C polymorphic site was significantly hypomethylated in SCZ, BD, and their first degree relatives compared to the controls. Cytosine methylation of HTR2A at T102C polymorphic site in DNA derived from the saliva can potentially be used as a diagnostic, prognostic, and/or therapeutic biomarker in SCZ and BD. However, these preliminary observations need to be replicated in other populations with a larger sample size to be considered for clinical applications. (C) 2011 Wiley-Liss, Inc.