Genetic and Inflammatory Factors in Anemia in the Elderly

描述（由申请人提供）：贫血已越来越被认为是老年人发病率和死亡率的主要因素。虽然贫血是与65岁以上患者生存率降低相关的独立危险因素，但至少有三分之一的患者贫血的病因尚不清楚，其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，并注意合并症的贡献，包括原发性血液学和非血液学合并症，应提供关键的干预措施，将提高老年人群的生存和生活质量的切入点。退伍军人老龄化队列研究（VACS）是一项观察性研究，包括3，213名患有艾滋病毒感染的退伍军人和3，161名人口统计学上相似的退伍军人。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。小组参加了电话采访，病人和供应商的焦点小组，组织收集。还启动了一项针对血液和DMA库的大型子研究。超过65%的VACS受试者是黑人或拉丁美洲人，中位年龄为50岁。由于退伍军人健康管理局（VHA）是一个基本上封闭的护理系统，我们享受近乎完整的数据收集和随访。VHA为该项目提供了大量支持，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援助。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阴性患者人群死亡的一个独立风险因素。有趣的是，两组中大红细胞症患者的风险比最高，尽管这两组中MCV升高的原因可能不同。衰老和HIV都与与虚弱相关的循环细胞因子水平升高有关，即TNF和IL-6。慢性炎症也与影响巨噬细胞迁移抑制因子（MIF）基因水平的多态性有关，该基因可诱导TNF。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了一种促炎症状态，并伴有炎症贫血。我们认为，艾滋病毒诱导的虚弱状态类似于老年人更频繁和更早的贫血，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.描述队列人群中贫血的年龄分层病因。2.描述慢性促炎状态在年龄分层贫血发病率中的作用。3.描述遗传多态性在预测促炎症状态发展中的作用。

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.