Šerý Omar, Hlinecká Lýdia, Balcar Vladimir J, Janout Vladimir, Povova Jana
Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science, Masaryk University, Brno, Czech Republic.
Discipline Anatomy and Histology and Bosch Institute, School of Medical Sciences, Sydney Medical School, The University of Sydney NSW, Australia.
Neuro Endocrinol Lett. 2014;35(8):691-6.
The aim of our current research project is to further evaluate the role of risk factors in the pathogenesis of Alzheimer's disease; these include genetic variations, environmental factors and lifestyle issues.
We have been conducting an association study on 373 patients with Alzheimer's disease and 286 unrelated control individuals. The occurrence and the age of onset of diabetes and cardiovascular diseases were evaluated in both groups. Apolipoprotein E genotype was analyzed in all subjects by PCR method.
We report that, in Czech population carrying ApoE4 allele increases risk of Alzheimer's disease 2.1-fold and genotype E4E4 increases the risk 8.4-fold. We have also identified a significant association between ApoE4 allele, Alzheimer's disease and hypertension. Hypertensive subjects with the ApoE4 allele have 1.5-fold greater risk of Alzheimer's disease. Thus, hypertension together with ApoE4 allele translates into 1.5-fold higher risk of AD. The most intriguing original finding in the present study is that Alzheimer's disease patients have significantly later onset of diabetes, hypertension and stroke in comparison with control subjects. This effect was not influenced by ApoE genotype. The diabetes appeared in AD patients on average more than 10 years later than in the control subjects (p<0.0001), hypertension was diagnosed 14 years later in AD patients (p<0.00001) and stroke occurred on average 6 years later (p<0.005), compared to the control group.
Overall, in addition to the above novel findings, our study expands the data base on risk factors that could be used in near future when testing for the genetic risk of Alzheimer's disease.
我们当前研究项目的目的是进一步评估风险因素在阿尔茨海默病发病机制中的作用；这些因素包括基因变异、环境因素和生活方式问题。
我们对373例阿尔茨海默病患者和286名无亲缘关系的对照个体进行了关联研究。评估了两组中糖尿病和心血管疾病的发生情况及发病年龄。通过聚合酶链反应（PCR）方法分析了所有受试者的载脂蛋白E基因型。
我们报告，在捷克人群中，携带载脂蛋白E4等位基因会使患阿尔茨海默病的风险增加2.1倍，而E4E4基因型会使风险增加8.4倍。我们还发现载脂蛋白E4等位基因、阿尔茨海默病和高血压之间存在显著关联。携带载脂蛋白E4等位基因的高血压受试者患阿尔茨海默病的风险高1.5倍。因此，高血压与载脂蛋白E4等位基因共同导致患阿尔茨海默病风险高出1.5倍。本研究中最引人关注的原始发现是，与对照受试者相比，阿尔茨海默病患者患糖尿病、高血压和中风的发病时间明显更晚。这种效应不受载脂蛋白E基因型的影响。与对照组相比，阿尔茨海默病患者出现糖尿病平均比对照受试者晚10多年（p<0.0001），高血压在阿尔茨海默病患者中诊断出的时间晚14年（p<0.00001），中风平均发生时间晚6年（p<0.005）。
总体而言，除上述新发现外，我们的研究扩展了风险因素的数据库，这些数据在未来检测阿尔茨海默病遗传风险时可能会用到。
