Matigian N, Windus L, Smith H, Filippich C, Pantelis C, McGrath J, Mowry B, Hayward N
Queensland Centre for Mental Health Research, Herston, QLD, Australia.
Mol Psychiatry. 2007 Sep;12(9):815-25. doi: 10.1038/sj.mp.4001998. Epub 2007 Apr 17.
To identify genes dysregulated in bipolar disorder (BD1), we carried out global gene expression profiling using whole-genome microarrays. To minimize genetic variation in gene expression levels between cases and controls, we compared expression profiles in lymphoblastoid cell lines from monozygotic twin pairs discordant for the disease. We identified 82 genes that were differentially expressed by >or=1.3-fold in three BD1 cases compared to their co-twins, and which were statistically (P<or=0.05) differentially expressed between the groups of BD1 cases and controls. Using quantitative reverse transcriptase-polymerase chain reaction, we confirmed the differential expression of some of these genes, including: KCNK1, MAL, PFN2, TCF7, PGK1 and PI4KCB, in at least two of the twin pairs. In contrast to the findings of a previous study by Kakiuchi and colleagues with similar discordant BD1 twin design, our data do not support the dysregulation of XBP1 and HSPA5. From pathway and gene ontology analysis, we identified upregulation of the WNT signalling pathway and the biological process of apoptosis. The differentially regulated genes and pathways identified in this study may provide insights into the biology of BD1.
为了鉴定双相情感障碍（BD1）中失调的基因，我们使用全基因组微阵列进行了全基因组基因表达谱分析。为了尽量减少病例组和对照组之间基因表达水平的遗传变异，我们比较了来自同卵双胞胎对中患病人和未患病人的淋巴母细胞系的表达谱。我们鉴定出82个基因，与同卵双胞胎中的未患病人相比，在3例BD1患者中差异表达≥1.3倍，并且在BD1病例组和对照组之间具有统计学差异（P≤0.05）。使用定量逆转录-聚合酶链反应，我们证实了其中一些基因（包括KCNK1、MAL、PFN2、TCF7、PGK1和PI4KCB）在至少两对双胞胎中差异表达。与Kakiuchi及其同事之前一项采用类似BD1不一致双胞胎设计的研究结果相反，我们的数据不支持XBP1和HSPA5失调。通过通路和基因本体分析，我们鉴定出WNT信号通路上调以及细胞凋亡的生物学过程。本研究中鉴定出的差异调节基因和通路可能为BD1的生物学机制提供见解。
