Serotonin receptor 2C (HTR2C) and schizophrenia:: Examination of possible medication and genetic influences on expression levels
Serotonin receptor 2C (HTR2C) and schizophrenia:: Examination of possible medication and genetic influences on expression levels
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DOI：
10.1002/ajmg.b.30151
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发表时间：
2005-04-05
影响因子：
2.8
通讯作者：
Jazin, E
中科院分区：
文献类型：
--
作者：
Castensson, A;Åberg, K;Jazin, E
5-羟色胺受体 2C (HTR2C) 基因由于参与前额皮质多巴胺活性的调节而在精神分裂症中引起关注。我们之前报道过精神分裂症患者前额皮质中 HTR2C mRNA 水平的表达降低。这里对 mRNA 表达水平的变异性进行了更密切的评估，与启动子单倍型和患者接受的抗精神病药物治疗有关。 HTR2C mRNA 的减少存在于接受抗精神病药治疗的个体和死亡时未接受治疗的患者中，表明较低的表达不是短期药物效应。使用三个启动子多态性来构建单倍型。没有 SNP 显示与该疾病的基因型或单倍型关联。 HTR2C 基因表达不受单倍型影响，精神分裂症患者的表达下降在所有单倍型组合（双倍型）中相似。我们的结论是，精神分裂症中HTR2C表达的降低可能与疾病机制有关，而不是与药物治疗有关。 HTR2C 表达的疾病相关变化与我们样本中分型的启动子变体无关，但可能是由于其他调控变体或反式作用因子所致。 (c) 2005 年 Wiley-Liss, Inc.
The serotonin receptor 2C (HTR2C) gene is of interest in schizophrenia due to its involvement in regulation of dopamine activity in the prefrontal cortex. We have previously reported a decreased expression of HTR2C mRNA levels in the prefrontal cortex of schizophrenia patients. The variability in mRNA expression levels is evaluated here more closely in relation to promoter haplotypes and neuroleptic treatment received by the patients. The decrease in HTR2C mRNA was present in neuroleptic treated individuals and in patients untreated at death, indicating that the lower expression is not a short-term medication effect. Three promoter polymorphisms were used to construct haplotypes. No SNP displayed genotypic or haplotypic association with the disease. Gene expression of HTR2C was not affected by haplotype and the expression decrease in schizophrenia patients was similar in all haplotype combinations (diplotypes). We conclude that the decrease in HTR2C expression in schizophrenia may be related to the disease mechanism rather than to drug treatment. The disease related changes in HTR2C expression are not related to the promoter variants typed in our sample, but could be due to other regulatory variants or transacting factors. (c) 2005 Wiley-Liss, Inc.