Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Neurosci Lett. 2011 Aug 21;501(1):41-4. doi: 10.1016/j.neulet.2011.06.038. Epub 2011 Jun 29.
The protein kinase AKT1 belongs to the Akt family and is a potent mediator of cell growth and survival and fully activated when phosphorylated. The AKT family has been found to be phosphorylated to a lesser extent in the dopaminergic cells of Parkinson's disease patients compared to control individuals, which might influence cell survival. Several publications support the implication of AKT1 in disorders of the dopaminergic system including bipolar disease and schizophrenia. In 2008 an association study performed in a Greek Parkinson's disease case-control material reported the identification of a protective AKT1 haplotype. Based on their work we have performed a replication study in a Swedish Parkinson's disease cohort. We genotyped the four single nucleotide polymorphims (SNPs): rs2494743, rs2498788, rs2494746 and rs1130214 in a case-control material consisting of 243 Parkinson patients and 315 controls. We did not find any associations with Parkinson's disease for either the individual SNPs or any of the haplotypes. In contrast to previously published results, our data do not support the hypothesis of genetic variants in AKT1 confering protection against Parkinson's disease.
蛋白激酶 AKT1 属于 Akt 家族，是细胞生长和存活的有力介质，当磷酸化时完全激活。与对照组相比，帕金森病患者的多巴胺能细胞中 AKT 家族的磷酸化程度较低，这可能会影响细胞存活。有几项出版物支持 AKT1 参与包括双相情感障碍和精神分裂症在内的多巴胺能系统疾病。2008 年，在一项针对希腊帕金森病病例对照材料的关联研究中报告了 AKT1 单倍型的保护性鉴定。基于他们的工作，我们在瑞典帕金森病队列中进行了一项复制研究。我们对四个单核苷酸多态性（SNPs）进行了基因分型：rs2494743、rs2498788、rs2494746 和 rs1130214，该研究包含 243 名帕金森病患者和 315 名对照。我们没有发现任何与帕金森病相关的单个 SNP 或任何单倍型的关联。与先前发表的结果相反，我们的数据不支持 AKT1 中的遗传变异赋予帕金森病保护作用的假设。
