Sims R, Hollingworth P, Moskvina V, Dowzell K, O'Donovan M C, Powell J, Lovestone S, Brayne C, Rubinsztein D, Owen M J, Williams J, Abraham R
Department of Psychological Medicine, Cardiff University School of Medicine, Heath Park, Cardiff CF144XN, UK.
Neurosci Lett. 2009 Sep 11;461(1):54-9. doi: 10.1016/j.neulet.2009.05.051. Epub 2009 May 27.
Psychotic symptoms are common in individuals with Alzheimer's disease (AD), and define a phenotype associated with more rapid cognitive and functional decline. Evidence suggests that psychotic symptoms may be influenced by genetic factors, and recent studies in schizophrenia, bipolar affective disorder (BPAD) and Alzheimer's disease with psychosis (AD+P) suggest that psychosis susceptibility or modifier genes may act across diseases. We hypothesised that oligodendrocyte lineage transcription factor 2 (OLIG2), a regulator of white matter development and a candidate gene for schizophrenia, may also be associated with psychotic symptoms in AD. We genotyped 11 SNPs in OLIG2 previously tested for association with schizophrenia [L. Georgieva, V. Moskvina, T. Peirce, N. Norton, N.J. Bray, L. Jones, P. Holmans, S. Macgregor, S. Zammit, J. Wilkinson, H. Williams, I. Nikolov, N. Williams, D. Ivanov, K.L. Davis, V. Haroutunian, J.D. Buxbaum, N. Craddock, G. Kirov, M.J. Owen, M.C. O'Donovan, Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility to schizophrenia, Proc. Natl. Acad. Sci. U.S.A. 103 (33) (2006) 12469-12474] and tested these for association with AD and AD+P. Significant evidence for association of psychotic symptoms within cases was identified for two SNPs, rs762237 (allelic P=0.002, OR=1.42, corrected P=0.019) and rs2834072 (allelic P=0.004, OR=1.41, corrected P=0.05).
精神病性症状在阿尔茨海默病（AD）患者中很常见，并且定义了一种与认知和功能衰退更快相关的表型。有证据表明，精神病性症状可能受遗传因素影响，最近在精神分裂症、双相情感障碍（BPAD）以及伴有精神病性症状的阿尔茨海默病（AD+P）中的研究表明，精神病易感性或修饰基因可能在多种疾病中发挥作用。我们推测，少突胶质细胞谱系转录因子2（OLIG2），一种白质发育的调节因子以及精神分裂症的候选基因，可能也与AD中的精神病性症状相关。我们对OLIG2中先前检测与精神分裂症相关联的11个单核苷酸多态性（SNP）进行了基因分型[L. 乔治耶娃、V. 莫斯科维娜、T. 皮尔斯、N. 诺顿、N.J. 布雷、L. 琼斯、P. 霍尔曼斯、S. 麦格雷戈、S. 扎米特、J. 威尔金森、H. 威廉姆斯、I. 尼科洛夫、N. 威廉姆斯、D. 伊万诺夫、K.L. 戴维斯、V. 哈鲁图尼安、J.D. 布克斯鲍姆、N. 克拉多克、G. 基洛夫、M.J. 欧文、M.C. 奥多诺万，少突胶质细胞谱系转录因子2（OLIG2）及相互作用基因影响精神分裂症易感性的趋同证据，《美国国家科学院院刊》103(33)(2006)12469 - 12474]，并检测这些SNP与AD及AD+P的关联性。在病例中，确定了两个SNP（rs762237，等位基因P = 0.002，比值比[OR]=1.42，校正后P = 0.019；以及rs2834072，等位基因P = 0.004，OR = 1.41，校正后P = 0.05）与精神病性症状存在显著关联证据。
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