Masri Inas, Salami Ali, El Shamieh Said, Bissar-Tadmouri Nisrine
Department of Medical Laboratory Technology, Faculty of Health Sciences, Beirut Arab University, Beirut, Lebanon.
Rammal Hassan Rammal Research Laboratory, Physio-Toxicity (PhyTox) Research Group, Lebanese University, Faculty of Sciences (V), Nabatieh, Lebanon.
Curr Aging Sci. 2020;13(2):162-168. doi: 10.2174/1874609812666191019143237.
Alzheimer's Disease (AD) is a multifactorial disease affected by various factors including genetics. Although APOE is considered the major and strongest genetic risk factor, other genetic factors such as rs3851179G>A in PICALM have been reported despite that not being fully clear.
We first aimed to investigate the correlation between rs3851179G>A in PICALM and AD in Lebanese individuals affected with AD. Then, we further investigated its overall effect in five different populations from the Mediterranean region (Turkey, Italy, Spain, France and ours) through performing a meta-analysis.
We investigated the relationship between the rs3851179G>A and AD in 109 Lebanese individuals (54% affected with AD) using allele-specific PCR. Sanger Sequencing was also used to verify genotyping.
Using a multiple logistic regression model adjusted for many covariates, only rs3851179G>A showed a negative correlation with AD (OR=0.28, P=0.04 and OR=0.07, P=0.01 for GA and AA, respectively). To go further, a meta-analysis was conducted using studies on 3,619 participants from five different populations that belong to countries surrounding the Mediterranean (Turkey, Italy, Spain, France and ours). The sensitivity test showed no genetic heterogeneity for rs3851179G>A in the pooled analysis (P=0.44 and I=0%) and in each individual study (P>0.05). Using an additive model, our results showed a significant association between rs3851179G>A and AD (OR=0.91, P=0.003). The funnel plot was a symmetrical inverted funnel and no significant publication bias was found for our model (P=0.46).
The rs3851179A allele in PICALM tends to have a protective factor against AD in the Mediterranean region.
阿尔茨海默病（AD）是一种受多种因素影响的多因素疾病，包括遗传学因素。虽然载脂蛋白E（APOE）被认为是主要且最强的遗传风险因素，但其他遗传因素，如磷脂酰肌醇结合网格蛋白组装蛋白（PICALM）基因中的rs3851179G>A，尽管尚未完全明确，但也已有报道。
我们首先旨在研究黎巴嫩AD患者中PICALM基因的rs3851179G>A与AD之间的相关性。然后，我们通过进行荟萃分析，进一步研究其在来自地中海地区的五个不同人群（土耳其、意大利、西班牙、法国以及我们的研究对象）中的总体效应。
我们使用等位基因特异性PCR研究了109名黎巴嫩个体（54%为AD患者）中rs3851179G>A与AD之间的关系。桑格测序也用于验证基因分型。
使用针对多种协变量进行调整的多元逻辑回归模型，仅rs3851179G>A与AD呈负相关（GA和AA基因型的比值比分别为OR=0.28，P=0.04和OR=0.07，P=0.01）。为进一步研究，我们对来自地中海周边五个不同国家（土耳其、意大利、西班牙、法国以及我们的研究对象）的3619名参与者的研究进行了荟萃分析。敏感性检验显示，在汇总分析（P=0.44，I²=0%）以及每个个体研究（P>0.05）中，rs3851179G>A均无基因异质性。使用加性模型，我们的结果显示rs3851179G>A与AD之间存在显著关联（OR=0.91，P=0.003）。漏斗图呈对称的倒漏斗形，我们的模型未发现显著的发表偏倚（P=0.46）。
PICALM基因中的rs3851179A等位基因在地中海地区倾向于对AD具有保护作用。
