PREVALENCE AND SPECTRUM OF B12 DEFICIENCY IN THE AGED

老年人维生素B12的患病率很高（10-20%） （钴胺素）缺乏症，但这种临床后果 不足之处仍然未知。血清甲基丙二酸升高， 总同型半胱氨酸是最敏感和具体的措施， 临床缺陷高同型半胱氨酸血症已被发现是一种 年轻人血管疾病独立危险因素 人口。本提案的一个主要目标是确定 钴胺素缺乏引起的高同型半胱氨酸血症是否 与心血管疾病相关， 妇女健康与老龄化研究所 Study.还将确定是否存在钴胺素缺乏症， 甲基丙二酸和/或总高半胱氨酸水平升高导致 巨幼细胞性贫血和/或振动感觉障碍， 平衡将确定标准复合维生素使用的效果 维生素B12缺乏症或叶酸缺乏症的患病率 代谢物。钴胺素状态与常见的 不耐热亚甲基四氢叶酸还原酶多态性 将在老年门诊人群中进行研究， 患有神经系统疾病的缺陷受试者或患有极度 高水平的同型半胱氨酸和巨幼细胞性贫血它还将 确定纯合不耐热突变是否导致 甲硫氨酸负荷后同型半胱氨酸水平异常。聚合酶 将使用基于链式反应的方法对受试者进行基因分型， 稳定同位素稀释气相色谱-质谱分析 将用于定量甲基丙二酸和总 同型半胱氨酸在食物叶酸强化计划完全完成后， 自1998年以来，数百万美国老年人 未经治疗的钴胺素缺乏症将暴露于叶酸强化 食物这项建议旨在调查临床后果 维生素B12缺乏症，以改善 诊断和替代治疗。

The elderly have a high prevalence (10-20%) of vitamin B12 (cobalamin) deficiency, but the clinical consequences of this deficiency are still unknown. Elevated serum methylmalonic acid and total homocysteine are the most sensitive and specific measures of clinical deficiency. Hyperhomocysteinemia has been found to be an independent risk factor for vascular disease in younger populations. A major objective of this proposal is to determine whether hyperhomocysteinemia due to cobalamin deficiency is correlated with cardiovascular disease in a large ethnically diverse female elderly population from the Women's Health and Aging Study. It will also be determined whether cobalamin deficiency with elevated methylmalonic acid and/or total homocysteine levels causes megaloblastic anemia and/or disorders of vibration sense and balance. The effect of standard multivitamin use will be determined on the prevalence of cobalamin or folate deficiency or elevated metabolites. The interaction between cobalamin status and a common polymorphism for thermolabile methylenetetrahydrofolate reductase will be studied in an elderly outpatient population, in cobalamin deficient subjects with neurologic disease or those with extremely high levels of homocysteine and megaloblastic anemia. It will also be determined whether the homozygous thermolabile mutations cause an abnormal post methionine load homocysteine level. Polymerase chain reaction based methods will be used to genotype subjects and stable isotope dilution gas chromatography-mass spectrometry assays will be used to quantitate methylmalonic acid and total homocysteine. After the food folate fortification program is fully implemented in 1998, millions of elderly Americans with previously untreated cobalamin deficiency will be exposed to folate fortified food. This proposal seeks to investigate the clinical consequences of cobalamin deficiency in the elderly in order to improve diagnosis and replacement therapy for these individuals.