Monoallelic and unequal allelic expression of the HTR2A gene in human brain and peripheral lymphocytes
Monoallelic and unequal allelic expression of the HTR2A gene in human brain and peripheral lymphocytes
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DOI：
10.1016/j.biopsych.2006.06.024
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发表时间：
2006-12-15
影响因子：
10.6
通讯作者：
Arinami, Tadao
中科院分区：
文献类型：
--
作者：
Fukuda, Yoshiko;Koga, Minori;Arinami, Tadao
背景资料：5-羟色胺2A受体（HTR 2A）基因的102 T/C多态性与精神分裂症及其他疾病和表型有关。已发现改变的HTR 2A表达与几种神经精神疾病有关，包括抑郁症和精神分裂症。对死后大脑中HTR 2A信使RNA（mRNA）和蛋白质表达的研究表明，102 C等位基因的转录活性可能低于T等位基因。然而，平等表达的两个等位基因也reported.Methods：我们进行了引物延伸试验，以测量等位基因特异性HTR 2A转录mRATA分离的前额叶皮层的31个人与精神分裂症和外周血淋巴细胞（PBL）的31个健康个体杂合子为102 T/C的相对表达。结果：DNA和mRNA分析表明，HTR 2A基因在9个家系的外周血淋巴细胞中有表达，但表达水平低于102 T基因。与在脑中观察到的双等位基因表达相反，HTR 2A的单等位基因表达在PBL中是常见的。然而，一个家庭的研究表明，印迹是不负责的单等位基因的表达在PBLs.Conclusions：本研究揭示了HTR 2A的表达，这使得等位基因和表等位基因分析的遗传药理学和药物基因组学研究HTR 2A的组织特异性修改。
Background: The 102T/Cpolymorpbism of the serotonin 2A receptor (HTR2A) gene is reported to be associated with schizophrenia and other diseases and phenotypes. Altered HTR2A expression has been found in relation to several neuropsychiatric conditions, including depression and schizophrenia. Studies of expression of HTR2A messenger RNA (mRNA) and protein in postmortem brains suggest that the 102C allele might be less transcriptionally active than the T allele. However, equal expression of both alleles has also been reported.Methods: We performed primer extension assays to measure relative expression of allele-specific HTR2A transcripts in mRATAs isolated from the prefrontal cortex of 31 individuals with schizophrenia and from peripheral lymphocytes (PBLs) of 31 healthy individuals heterozygous for 102T/C. We also examined the allele transmission pattern of HTR2A in PBLs of nine families.Results: Analyses of DNA and mRNA revealed that 102C is expressed but at lower levels than 102T in brains. In contrast to the biallelic expression observed in brains, monoallelic expression of HTR2A was common in PBLs. However, a family study revealed that imprinting was not responsible for the monoallelic expression in PBLs.Conclusions: The present study revealed a tissue-specific modification of HTR2A expression, which makes allelic and epiallelic analyses necessary for genetic epidemologic and pharmacogenomic studies of HTR2A.