Associations between putative risk factors and Alzheimer' s disease accordongs to gene polymorphisms using a large case control study

我们从基因水平评估了阿尔茨海默病(AD)可能的危险因素与阿尔茨海默病(AD)的关系。受试者为407名根据NINCDS-ADRDA标准诊断为阿尔茨海默病(AD)的患者(男性168名，女性239名，发病年龄69±10岁)。受试者配偶398人(男16 2人，女2 36人，年龄69±9岁)为对照组。风险因素访谈是专门为这项研究开发的，以评估17个假定的风险因素。采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法检测载脂蛋白E基因多态性。用Long Read Tower Sequencer的聚合酶链式反应片段分析软件对极低密度脂蛋白受体基因(VLDLr)的三联体(CGG)重复序列进行基因分型。用SAS统计分析软件进行估计优势比和多因素Logistic回归分析，评价其相关性。这项研究是在获得受试者或他们的监护人的书面知情同意后进行的。基因分析显示，AD与VLDLr和APOE相关，e4等位基因的优势比为2.98。AD组VLDLr基因5重复等位基因频率显著高于对照组(P<0.04)。5重复等位基因的优势比为1.56(95%CI为1.32~1.78)。年龄、AD家族史、受教育年限、午睡和伴侣死亡等可能是AD的危险因素。虽然大多数危险因素与基因多态性没有交互作用，但发病年龄与APOE有关，但与VLDLr无关。限量午睡60min对AD的发生有保护作用，尤其是APOE e4基因携带者(OR=0.49，95%CI：0.33~0.73)。

We evaluated that an association between putative risk factors and Alzheimer's disease (AD) according gene p olym orp hisms.The subjects were 407 patients (168 men and 239 women :age at onset 69±10) with a diagnosis of probable AD based on the NINCDS-ADRDA criteria. Three hundred and ninety eight spouses (162 men and 236 women : age 69±9) of the subjects served as control. The risk factor interview was developed specifically for this study to assess 17 putative risk factors. APOE gene polymorphisms were determined by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The triplet (CGG) repeat polymorphism of very low density lipoprotein receptor gene (VLDLr) was genotyped by the PCR fragment analysis software of Long Read Tower sequencer. The estimating odds ratio and the multiple logistic analysis were performed by SAS statistic analysis package to evaluate the association. This study was conducted after obtaining written informed consent from the subjects or their guardians.The genetic analysis revealed the AD was associated with VLDLr as well as APOE : he odds ratio was 2.98 for the e4 allele. The frequency of the 5-repeat ; allele ofVLDLr was significantly higher in AD than in control(p<0.04). The odds ratio for 5-repeat allele was 1.56 (95 % CI 1.32-1.78). Some of putative risk factors including aging, family history of AD, education years, napping and death of partner were confirmed as risk factors for AD. Though most of these risk factors were not interactive with gene polymorphisms, onset age was associated with APOE but not VLDLr. And limited habitual napping for up to 60 min had a protective effect against the development of AD especially for carriers of the APOE e4 (OR=0.49, 95 % CI :0.33-0.73).