Hamilton Gillian, Proitsi Petra, Jehu Luke, Morgan Angharad, Williams Julie, O'Donovan Michael C, Owen Michael J, Powell John F, Lovestone Simon
MRC Centre for Neurodegeneration Research, Department of Neuroscience, Institute of Psychiatry, Kings College London, Denmark Hill, London, UK.
Am J Med Genet B Neuropsychiatr Genet. 2007 Jun 5;144B(4):508-16. doi: 10.1002/ajmg.b.30503.
Epidemiological evidence supports the existence of a possible link between type II diabetes mellitus (T2DM) and late-onset Alzheimer's disease (LOAD). Polymorphisms from candidate genes for T2DM were genotyped in a two-stage approach to identify novel risk factors for LOAD. One hundred fifty-two polymorphisms were initially genotyped in a case:control cohort: nine SNPs showed individual association with disease status under at least one genetic model, while an additional two SNPs showed a haplotype association. In a replication study, we confirmed significant association of SNPs within three genes--PPARgamma, SOS2, and PCK1--with Alzheimer's disease. In particular, our data suggest that the effect of variants within these genes might be influenced by gender.
流行病学证据支持2型糖尿病（T2DM）与晚发型阿尔茨海默病（LOAD）之间可能存在联系。采用两阶段方法对T2DM候选基因的多态性进行基因分型，以确定LOAD的新风险因素。最初在病例对照队列中对152个多态性进行基因分型：9个单核苷酸多态性（SNP）在至少一种遗传模型下显示出与疾病状态的个体关联，另外2个SNP显示出单倍型关联。在一项重复研究中，我们证实了三个基因（PPARγ、SOS2和PCK1）内的SNP与阿尔茨海默病存在显著关联。特别是，我们的数据表明这些基因内变异的影响可能受性别影响。
