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VRK2 gene expression in schizophrenia, bipolar disorder and healthy controls

机译:VRK2基因在精神分裂症,躁郁症和健康对照组中的表达

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Background Common variants in the Vaccinia-related kinase 2 ( VRK2 ) gene have been associated with schizophrenia, but the relevance of its encoded protein VRK2 in the disorder remains unclear. Aims To identify potential differences in VRK2 gene expression levels between schizophrenia, bipolar disorder, psychosis not otherwise specified (PNOS) and healthy controls. Method VRK2 mRNA level was measured in whole blood in 652 individuals (schizophrenia, n = 201; bipolar disorder, n = 167; PNOS, n = 61; healthy controls, n = 223), and compared across diagnostic categories and subcategories. Additionally, we analysed for association between 1566 VRK2 single nucleotide polymorphisms and mRNA levels. Results We found lower VRK2 mRNA levels in schizophrenia compared with healthy controls ( P 10?12), bipolar disorder ( P 10?12) and PNOS ( P = 0.0011), and lower levels in PNOS than in healthy controls ( P = 0.0042) and bipolar disorder ( P = 0.00026). Expression quantitative trait loci in close proximity to the transcription start site of the short isoforms of the VRK2 gene were identified. Conclusions Altered VRK2 gene expression seems specific for schizophrenia and PNOS, which is in accordance with findings from genome-wide association studies. These results suggest that reduced VRK2 mRNA levels are involved in the underlying mechanisms in schizophrenia spectrum disorders.
机译:背景牛痘相关激酶2(VRK2)基因的常见变异与精神分裂症有关,但尚不清楚其编码的蛋白质VRK2在该疾病中的相关性。目的确定精神分裂症,躁郁症,其他未指明的精神病(PNOS)和健康对照者之间VRK2基因表达水平的潜在差异。方法测量了652名个体(精神分裂症,n = 201;躁郁症,n = 167; PNOS,n = 61;健康对照组,n = 223)的全血中VRK2 mRNA的水平,并比较了诊断类别和亚类别。此外,我们分析了1566 VRK2单核苷酸多态性与mRNA水平之间的关联。结果我们发现精神分裂症患者的VRK2 mRNA水平低于健康对照组(P <10?12),双相情感障碍(P <10?12)和PNOS(P = 0.0011),而PNOS的水平低于健康对照组(P = 0.0042)和双相情感障碍(P = 0.00026)。鉴定出与VRK2基因的短同工型的转录起始位点非常接近的表达定量性状基因座。结论改变的VRK2基因表达似乎对精神分裂症和PNOS具有特异性,这与全基因组关联研究的结果一致。这些结果表明,降低的VRK2 mRNA水平与精神分裂症谱系障碍的潜在机制有关。

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