Gene expression analysis in schizophrenia: Reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22
Gene expression analysis in schizophrenia: Reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22
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DOI：
10.1073/pnas.032069099
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发表时间：
2002-04-02
影响因子：
11.1
通讯作者：
Bahn, S
中科院分区：
文献类型：
--
作者：
Mimmack, ML;Ryan, M;Bahn, S
我们筛选了包含300个基因的定制候选基因cDNA阵列。所选择的基因要么与精神分裂症有关，根据目前对这种疾病的理解，在概念上有意义，要么位于高易感染色体位置。使用来自10个精神分裂症患者和10个对照组的前额叶皮层组织的阵列筛选显示，载脂蛋白L1 （apo L1）明显上调2.6倍。这一发现在一项盲法定量PCR研究中得到了交叉验证，该研究使用了斯坦利基金会（Stanley Foundation）在马里兰州贝塞斯达（Bethesda）收集的大脑前额皮质组织。该收集包括15名精神分裂症患者、15名双相情感障碍患者、15名重度抑郁症患者和15名对照个体，所有60个大脑在常规参数上都得到了很好的匹配，在精神分裂症和双相情感障碍组中使用了抗精神病药物。证实了精神分裂症患者载脂蛋白L1基因表达的显著上调。利用定量PCR技术，研究了apo L家族其他成员（apo L2- l6）的表达谱，发现apo L2和L4在精神分裂症中高度显著上调。研究结果随后在来自日本和新西兰的20个精神分裂症患者和20个对照组中得到了证实。载脂蛋白L蛋白属于高密度脂蛋白组，所有6个载脂蛋白L基因都位于染色体22q12上彼此靠近，染色体22q12是精神分裂症的一个确认的高易感位点，靠近与包括精神分裂症症状的心面快速综合征相关的区域。
We screened a custom-made candidate gene cDNA array comprising 300 genes. Genes chosen have either been implicated in schizophrenia, make conceptual sense in the light of the current understanding of the disease, or are located on high-susceptibility chromosome locations. The array screen using prefrontal cortex tissue from 10 schizophrenia and 10 control brains revealed robust up-regulation of apolipoprotein L1 (apo L1) by 2.6-fold. The finding was cross-validated in a blinded quantitative PCR study using prefrontal cortex tissue from the Stanley Foundation brain collection, Bethesda, MD. This collection consists of 15 schizophrenia, 15 bipolar disorder, 15 major depression, and 15 control individuals, all 60 brains being well-matched on conventional parameters, with antipsychotic drug exposure in the schizophrenia and bipolar disorder groups. Significant up-regulation of apo L1 gene expression in schizophrenia was confirmed. Using quantitative PCR, expression profiles of other members of the apo L family (apo L2-L6) were investigated, showing that apo L2 and L4 were highly significantly up-regulated in schizophrenia. Results were then confirmed in an independent set of 20 schizophrenia and 20 control brains from Japan and New Zealand. Apo L proteins belong to the group of high density lipoproteins, with all six apo L genes located in close proximity to each other on chromosome 22q12, a confirmed high-susceptibility locus for schizophrenia and close to the region associated with velocardiofacial syndrome that includes symptoms of schizophrenia.