Portland Veterans Affairs Medical Center, Oregon Health and Science University, Portland, OR.
Alzheimer Dis Assoc Disord. 2011 Jul-Sep;25(3):276-82. doi: 10.1097/WAD.0b013e31820a1d32.
Brain development in the early stages of life has been suggested to be one of the factors that may influence an individual's risk of Alzheimer disease (AD) later in life. Four microcephaly genes, which regulate brain development in utero and have been suggested to play a role in the evolution of the human brain, were selected as candidate genes that may modulate the risk of AD. We examined the association between single nucleotide polymorphisms tagging common sequence variations in these genes and risk of AD in two case-control samples. We found that the G allele of rs2442607 in microcephalin 1 was associated with an increased risk of AD (under an additive genetic model, P=0.01; odds ratio=3.41; confidence interval, 1.77-6.57). However, this association was not replicated using another case-control sample research participants from the Alzheimer Disease Neuroimaging Initiative. We conclude that the common variations we measured in the 4 microcephaly genes do not affect the risk of AD or that their effect size is small.
早期生命中的大脑发育被认为是可能影响个体日后患阿尔茨海默病（AD）风险的因素之一。四个小头畸形基因，这些基因在子宫内调节大脑发育，并被认为在人类大脑的进化中发挥作用，被选为可能调节 AD 风险的候选基因。我们在两个病例对照样本中研究了这些基因中常见序列变异的单核苷酸多态性标记与 AD 风险之间的关联。我们发现，小头畸形蛋白 1 中 rs2442607 的 G 等位基因与 AD 风险增加相关（在加性遗传模型下，P=0.01；优势比=3.41；置信区间，1.77-6.57）。然而，使用来自阿尔茨海默病神经影像学倡议的另一个病例对照样本研究参与者，我们没有复制这种关联。我们的结论是，我们在 4 个小头畸形基因中测量到的常见变异不会影响 AD 的风险，或者它们的效应大小很小。
