HEMOCHROMATOSIS--EPIDEMIOLOGY AND MOLECULAR MECHANISMS

遗传性血色病，一种以铁过量为特征的疾病 吸收导致糖尿病、心肌病、肝硬化， 关节病，可以说是最常见的临床重要的遗传 欧洲人的混乱 最近，HLA-H是HLA 1类基因， 与这种疾病的病因有关。 超过80%的 血色素沉着症患者对于C282 Y突变是纯合的。 化合物 C282 Y和H62 D的杂合子似乎具有增加的发病率， 疾病。 6万名成年人接受健康检查 在凯撒永久系统将进行筛选，确定血清 铁、铁结合能力、铁蛋白和HLA-H突变。 患者 被归类为患有血色病的患者将进行抽血， 铁的含量和铁的储存量。 这将建立 基因型、年龄、性别和临床状态之间的关系，以及 铁存储，并提供数据，可用于指导程序 血色素沉着症的筛查 杂合子是 更容易患上心血管疾病和其他疾病， 他们对缺铁性贫血的易感性较低 将使用广泛的凯撒永久数据库进行测试。 除了已知的那些，还将寻找血色素沉着病突变。 HLA-H基因产物可以像其它HLA 1类基因一样起作用， 结合肽并与蛋白质如β 2 微球蛋白，钙网蛋白，抗原相关转运蛋白 加工（TAP）和tapascin。 或者，它可以用作 信号分子，比如Fc受体。 确定HLA-H 基因产物的功能应该提供深入了解它的作用， 维持铁的体内平衡 这将通过使用 免疫沉淀含HLA-H的复合物，测定HLA-H Fc 受体信号传导特性和测量肽的结合， HLA-H的其他小分子。

Hereditary hemochromatosis, a disease characterized by excess iron absorption leading to diabetes, cardiomyopathy, cirrhosis, and arthropathies, is arguably the most common clinically important genetic disorder of Europeans. Recently an HLA Class 1 gene, HLA-H was implicated in the etiology of this disease. Over 80 percent of hemochromatosis patients are homozygous for a C282Y mutation. Compound heterozygotes for C282Y and H62D appear to have an increased incidence of the disease. Sixty-thousand adults undergoing health care screening in the Kaiser-Permanente system will be screened, determining serum iron, iron binding capacity, ferritin, and mutations in HLA-H. Patients classified as having hemochromatosis will be phlebotomized to remove excess iron and to measure iron stores. This will establish the relationship between genotype, age, sex and clinical state, and size of iron stores, and provide data that can be used to guide programs screening for hemochromatosis. The hypotheses that heterozygotes are more susceptible to cardiovascular disease and other disorders and that they are benefited by being less susceptible to iron deficiency anemia will be tested using the extensive Kaiser-Permanente database. Hemochromatosis mutations, other than those known, will be sought. The HLA-H gene product may function like other HLA class 1 genes, binding peptides and associating with proteins such as beta2 microglobulin, calreticulin, transporter associated with antigen processing (TAP) and tapascin. Alternatively, it may function as a signaling molecule, like the Fc receptor. Determining how the HLA-H gene product functions should provide insight into its role in maintaining iron homeostasis. This will be done by using immunoprecipitating HLA-H containing complexes, determining HLA-H Fc receptor signaling properties and measuring the binding of peptides and other small molecules by HLA-H.