Fukuda Yoshiko, Koga Minori, Arai Makoto, Noguchi Emiko, Ohtsuki Tsuyuka, Horiuchi Yasue, Ishiguro Hiroki, Niizato Kazuhiro, Iritani Shyuji, Itokawa Masanari, Arinami Tadao
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Biol Psychiatry. 2006 Dec 15;60(12):1331-5. doi: 10.1016/j.biopsych.2006.06.024. Epub 2006 Oct 25.
The 102T/C polymorphism 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.
We performed primer extension assays to measure relative expression of allele-specific HTR2A transcripts in mRNAs 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.
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.
The present study revealed a tissue-specific modification of HTR2A expression, which makes allelic and epiallelic analyses necessary for genetic epidemiologic and pharmacogenomic studies of HTR2A.
据报道，血清素2A受体（HTR2A）基因的102T/C多态性与精神分裂症及其他疾病和表型相关。已发现HTR2A表达改变与包括抑郁症和精神分裂症在内的多种神经精神疾病有关。对死后大脑中HTR2A信使核糖核酸（mRNA）和蛋白质表达的研究表明，102C等位基因的转录活性可能低于T等位基因。然而，也有报道称两个等位基因的表达相等。
我们进行了引物延伸分析，以测量从31例精神分裂症患者的前额叶皮质分离的mRNA以及31例102T/C杂合健康个体的外周淋巴细胞（PBL）中，等位基因特异性HTR2A转录本的相对表达。我们还研究了9个家庭的PBL中HTR2A的等位基因传递模式。
DNA和mRNA分析显示，102C在大脑中表达，但水平低于102T。与大脑中观察到的双等位基因表达相反，HTR2A在PBL中常见单等位基因表达。然而，一项家庭研究表明，印记并非PBL中单等位基因表达的原因。
本研究揭示了HTR2A表达的组织特异性修饰，这使得对HTR2A进行遗传流行病学和药物基因组学研究时，等位基因和表观等位基因分析成为必要。
