Alam Rizwan, Tripathi Manjari, Mansoori Nasim, Parveen Shama, Luthra Kalpana, Lakshmy Ramakrishnan, Sharma Subhadra, Arulselvi Subramanian, Mukhopadhyay Asok K
Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.
Department of Neurology, All India Institute of Medical Sciences, New Delhi, India.
Am J Alzheimers Dis Other Demen. 2014 Dec;29(8):769-76. doi: 10.1177/1533317514539541. Epub 2014 Jun 24.
Genetic polymorphism and epistasis play a role in etiopathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). In this case-control study, a total of 241 patients were included in the study to see the effect of paraoxonase 1 (PON1; rs662 and rs85460) and apolipoprotein E (ApoE) genes in altering the odds of having AD and VaD along with serum PON and lipid profile. The presence of at least 1 variant allele of rs662, but not rs85460, increased the risk of having AD by 1.8-fold (95% confidence interval [CI]: 0.97-3.40) and VaD by 3.09-fold (95% CI: 1.4-6.9). The interaction between PON1 genes (rs662 and rs85460) and ApoE genes showed synergistic epistasis in altering the odds of significantly having both AD and VaD. On the other hand, low serum level of high-density lipoprotein and low level of serum PON activity were found associated significantly (P ≤ .001 in both cases) only in patients with VaD as compared to healthy control.
基因多态性和上位性在阿尔茨海默病（AD）和血管性痴呆（VaD）的发病机制中起作用。在这项病例对照研究中，共有241名患者纳入研究，以观察对氧磷酶1（PON1；rs662和rs85460）和载脂蛋白E（ApoE）基因在改变患AD和VaD几率以及血清PON和血脂谱方面的作用。rs662至少存在1个变异等位基因，但rs85460不存在，使患AD的风险增加1.8倍（95%置信区间[CI]：0.97 - 3.40），患VaD的风险增加3.09倍（95%CI：1.4 - 6.9）。PON1基因（rs662和rs85460）与ApoE基因之间的相互作用在改变显著患AD和VaD的几率方面显示出协同上位性。另一方面，与健康对照相比，仅在VaD患者中发现血清高密度脂蛋白水平低和血清PON活性低与疾病显著相关（两种情况P均≤.001）。
