Genetic and Inflammatory Factors in Anemia in the Elderly

描述(申请人提供)：贫血已日益被认为是导致老年人发病率和死亡率的主要因素。虽然很明显，贫血是与65岁以上患者存活率降低有关的独立危险因素，但至少有三分之一的患者贫血的病因尚不清楚，导致身体衰退和死亡的发病机制也是未知的。更好地了解老年人贫血的病理生理学，关注原发血液病和非血液病并存疾病的作用，应该为改善老年人口的生存和生活质量的干预提供关键的切入点。退伍军人老龄化队列研究(VICS)是一项观察性研究，对象是3213名有艾滋病毒感染的退伍军人和3161名人口统计学上相似的未感染艾滋病毒的退伍军人。该数据库包括完整的电子病历数据和关于所有主题的年度自我完成调查。小组参与了电话采访、患者和提供者焦点小组以及组织收集。还启动了一项关于血液和DMA银行的大型子研究。超过65%的Vacs受试者是黑人或拉丁裔，年龄中值为50岁。由于退伍军人健康管理局(VHA)在很大程度上是一个封闭的医疗系统，我们享有近乎完整的数据收集和跟踪。VHA为该项目提供大量支持，包括住房、数据集、信息学、电话会议以及数据清理和存储方面的协助。这项研究已经提供了重要的数据，证实贫血是艾滋病毒阳性和艾滋病毒患者群体中死亡的独立风险因素。有趣的是，大细胞增多症患者的风险比在两组中都是最高的，尽管这两组中MCV升高的原因似乎很可能是不同的。衰老和艾滋病毒都与循环细胞因子水平的升高有关，这些细胞因子与虚弱有关，即肿瘤坏死因子和白介素6。慢性炎症也与影响巨噬细胞移动抑制因子(MIF)基因水平的多态性有关，MIF基因可诱导肿瘤坏死因子。我们的中心假设是，在没有营养缺乏的情况下，老年人的贫血通常反映出一种促炎状态，并伴随着炎症性贫血。我们认为，艾滋病毒会导致类似于老年人的虚弱状态，并更频繁和更早地出现贫血，这反映了与衰老相关的炎症过程的加速。我们的具体目标是： 1.队列人群贫血的年龄分层病因特征。2.探讨慢性促炎状态在年龄分层贫血发病率中的作用。3.探讨基因多态在预测促炎状态发展中的作用。

DESCRIPTION (provided by applicant): Anemia has become increasingly recognized as a major contributor to morbidity and mortality in the elderly. Although it is clear that anemia is an independent risk factor associated with reduced survival in patients over age 65, the etiology of anemia in at least one third of these patients is unknown, as is the pathogenesis by which it leads to physical decline and death. A better understanding of the pathophysiology of anemia in the elderly, with attention to the contribution of co-morbid disease, both primary hematologic and nonhematologic comorbidities, should provide critical entry points for interventions that will improve survival and quality of life in the elderly population. The Veterans Aging Cohort Study (VACS) is an observational study of 3,213 veterans with and 3,161 demographically similar veterans without HIV infection. The database includes full electronic medical record data and annual self-completed surveys on all subjects. Subsets have participated in telephone interviews, patient and provider focus groups, and tissue collection. A large substudy has also been initiated for blood and DMA banking. Over 65% of VACS subjects are black or Latino and the median age is 50 years. Because the Veterans Health Administration (VHA) is a largely closed system of care, we enjoy near complete data collection and follow-up. VHA provides substantial support for this project including housing, datasets, informatics, teleconferencing, and assistance with data cleaning, and storage. This study has already provided important data confirming that anemia is an independent risk factor for death in both the HIV+ and HIV- patient populations. Interestingly, the hazards ratio is highest in both groups for those patients with macrocytosis, although it seems quite possible that the causes of an elevated MCV in these two groups could be divergent. Both aging and HIV are associated with elevation in the level of circulating cytokines that are associated with frailty, namely TNF and IL-6. Chronic inflammation has also been linked with polymorphisms affecting levels of macrophage migration inhibitory factor (MIF) gene, which induces TNF. Our central hypothesis is that in the absence of nutritional deficiency, anemia in the elderly usually reflects a proinflammatory state with an associated anemia of inflammation. We would suggest that HIV induces a frail state similar to that seen in the elderly with a more frequent and earlier anemia that reflects an acceleration of the inflammatory process associated with aging. Our specific aims are: 1. To characterize the age-stratified etiology of anemia in the cohort population. 2. To characterize the role of a chronic proinflammatory state in the age-stratified incidence of anemia. 3. To characterize the role of genetic polymorphisms in predicting the development of a proinflammatory state.