Matera Maria G, Sancarlo Daniele, Panza Francesco, Gravina Carolina, D'Onofrio Grazia, Frisardi Vincenza, Longo Grazia, D'Ambrosio Luigi P, Addante Filomena, Copetti Massimiliano, Solfrizzi Vincenzo, Seripa Davide, Pilotto Alberto
Department of Medical Sciences, Geriatrics Unit & Gerontology-Geriatric Research Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
Age (Dordr). 2010 Sep;32(3):411-20. doi: 10.1007/s11357-010-9144-x. Epub 2010 Apr 20.
The most common apolipoprotein E (APOE) allelic variation is implicated in many age-related diseases and human longevity with controversial findings. We investigated the effect of APOE gene polymorphism on all-cause mortality in elderly patients taking into consideration the functional disability, cognitive impairment, malnutrition, and the occurrence of common age-related diseases. APOE genotypes were determined in 2,124 geriatric hospitalized patients (46.5% men and 53.5% women; mean age, 78.2 +/- 7.1 years; range, 65-100 years). At hospital admission, all patients underwent a comprehensive geriatric assessment to evaluate functional disability, cognitive status, nutritional status, and comorbidity. The main and secondary diagnoses at hospital discharge were also recorded. Mortality status was evaluated in all patients after a maximum follow-up of 5 years (range, from 1.26 to 5.23 years; median, 2.86 years). During the study period, 671 patients died (32.0%). At hospital admission, these patients showed a significant higher prevalence of cardiovascular diseases (56.3% vs 53.4%; p = 0.007), neoplasias (32.3% vs 13.7%; p < 0.001), and lower prevalence of neurodegenerative diseases (17.7% vs 20.7%; p < 0.001) than survived patients. Moreover, they also showed an higher prevalence of disability (52.0% vs 25.6%; p < 0.001), cognitive impairment (31.0% vs 18.8%; p < 0.001), and malnutrition (74.0% vs 46.1%; p < 0.001) than survived patients. In the overall study population, the APOE epsilon2 allele was significantly associated to neurodegenerative diseases (odds ratio = 0.59; 95% confidence interval (CI), 0.37-0.94). No significant association between the APOE polymorphism and disability, malnutrition, co-morbidity status, and with all-cause mortality was observed. In patients with cardiovascular diseases, however, a decreased risk of all-cause mortality was found in the epsilon2 allele carriers (hazard ratio = 0.56; 95% CI, 0.36-0.88). In this population, APOE allele variants might play a role on cardiovascular disease-related mortality.
最常见的载脂蛋白E(APOE)等位基因变异与许多年龄相关疾病和人类长寿有关,但其研究结果存在争议。我们在考虑功能残疾、认知障碍、营养不良以及常见年龄相关疾病发生情况的前提下,调查了APOE基因多态性对老年患者全因死亡率的影响。对2124名老年住院患者(男性占46.5%,女性占53.5%;平均年龄78.2±7.1岁;年龄范围65 - 100岁)进行了APOE基因分型。入院时,所有患者均接受了全面的老年综合评估,以评估功能残疾、认知状态、营养状况和合并症情况。同时记录了出院时的主要和次要诊断。在对所有患者进行最长5年的随访(随访时间范围为1.26至5.23年;中位数为2.86年)后,评估了死亡状态。在研究期间,671名患者死亡(占32.0%)。入院时,这些患者中心血管疾病的患病率显著高于存活患者(56.3%对53.4%;p = 0.007),肿瘤的患病率也显著高于存活患者(32.3%对13.7%;p < 0.001),而神经退行性疾病的患病率低于存活患者(17.7%对20.7%;p < 0.001)。此外,他们的残疾患病率(52.0%对25.6%;p < 0.001)、认知障碍患病率(31.0%对18.8%;p < 0.001)和营养不良患病率(74.0%对46.1%;p < 0.001)也高于存活患者。在整个研究人群中,APOE ε2等位基因与神经退行性疾病显著相关(比值比 = 0.59;95%置信区间(CI),0.37 - 0.94)。未观察到APOE基因多态性与残疾、营养不良、合并症状态以及全因死亡率之间存在显著关联。然而,在患有心血管疾病的患者中,发现ε2等位基因携带者的全因死亡风险降低(风险比 = 0.56;95% CI,0.36 - 0.88)。在该人群中,APOE等位基因变异可能在心血管疾病相关死亡率中起作用。