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

我们根据基因多态性评估了假定的危险因素与阿尔茨海默病（AD）之间的关系。受试者为407例患者（男性168例，女性239例，发病年龄69±10岁），根据NINCDS-ADRDA标准诊断为可能的AD。338名配偶（男162名，女236名，年龄69±9岁）作为对照组。风险因素访谈是专门为本研究开发的，以评估17个假定的风险因素。采用聚合酶链反应限制性片段长度多态性（PCR-RFLP）法测定APOE基因多态性。利用长读塔测序软件对极低密度脂蛋白受体基因（VLDLr）的三联体（CGG）重复多态性进行基因分型。采用SAS统计分析软件包进行比值比估计和多元logistic分析，评价相关性。本研究是在获得受试者或其监护人的书面知情同意后进行的。遗传分析显示，AD与VLDLr和APOE相关：e4等位基因的比值比为2.98。5重复的频率；AD患者中vldlr等位基因显著高于对照组（p<0.04）。5重复等位基因的优势比为1.56 （95% CI 1.32 ~ 1.78）。一些假定的危险因素包括年龄、AD家族史、受教育年限、睡眠和伴侣死亡被证实为AD的危险因素。虽然这些危险因素大多与基因多态性不相互作用，但发病年龄与APOE相关，而与VLDLr无关。有限的习惯性午睡长达60分钟对AD的发展有保护作用，特别是对APOE e4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).