MOLECULAR GENETICS ANALYSIS OF APOLIPOPROTEIN H IN SLE

描述：（改编自研究者摘要）载脂蛋白H（APOH） 是抗磷脂抗体结合的必需辅因子， 阴离子磷脂，表明APOH的结构变化 分子可能对自身抗体与 其结果是，它决定了血栓形成的结果。 基于 APOH目前的生理作用以及APOH基因 是遗传多态性的，研究人员假设， 确定磷脂相互作用结合位点的结构变化 对APOH分子的结合有显著影响， 抗磷脂自身抗体的亲和力和相关的 系统性红斑狼疮（SLE）患者血栓事件。 拟议的全面研究将建立已知的 结构和定量多态性的直接测序， APOH基因的表达部分（Aim 1）;检测新的和常见的遗传 APOH基因多态性（目的2）;进行体外表达研究 并检查各种APOH等位基因产物与阴离子的结合能力， 磷脂（目的3）;比较APOH的定量血浆水平 SLE患者和对照组之间的关系（目的4）;评估 APOH多态性和APOH的定量血浆水平（目的5）;确定 SLE患者中已知APOH多态性的频率分布， 控制（目标6）;并评估遗传定义之间的关系 APOH基因的结构多态性和数量多态性， 以及SLE患者抗磷脂抗体的发生情况（目的7）。 研究人员指出，拟议的研究将促进 APOH基因作用的鉴定和表征 抗磷脂抗体基因多态性与系统性红斑狼疮的关系 患者

DESCRIPTION: (Adapted from Investigator's Abstract) Apolipoprotein H (APOH) is an essential cofactor for the binding of antiphospholipid antibodies to anionic phospholipids, suggesting that structural variations in the APOH molecule may have a significant impact on the binding of autoantibodies to their substrate; thus, determining the outcome of thrombosis. Based upon the current physiologic role of APOH and the information that the APOH gene is genetically polymorphic, the investigators hypothesize that genetically determined structural changes in the phospholipid interaction binding sites on the APOH molecule have a significant impact in determining the binding affinity of antiphospholipid autoantibodies and the occurrence of associated thrombotic events in patients with systemic lupus erythematosus (SLE). The proposed comprehensive study will establish the molecular basis of known structural and quantitative polymorphism by direct sequencing of the expressed portion of the APOH gene (Aim 1); detect new and common genetic polymorphisms in the APOH gene (Aim 2); perform in vitro expression studies and examine the binding abilities of various APOH allele products to anionic phospholipids (Aim 3); compare the quantitative plasma levels of APOH between SLE patients and controls (Aim 4); evaluate the relationship between APOH polymorphisms and quantitative plasma levels of APOH (Aim 5); determine the frequency distributions of known APOH polymorphisms in SLE patients and controls (Aim 6); and evaluate the relationship between genetically defined structural polymorphisms, and quantitative polymorphism in the APOH gene, and the occurrence of antiphospholipid antibodies in SLE patients (Aim 7). The investigators state that the proposed studies will facilitate the identification and characterization of the role of APOH genetic polymorphisms in the prediction of the antiphospholipid antibodies in SLE patients.