GENETIC STUDY OF PROTEIN C DEFICIENCY AND THROMBOSIS

蛋白质 C 缺乏和血栓形成的遗传学研究

• 批准号: 6277197
• 负责人: EDWIN G BOVILL
• 金额: $ 2.62万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277197
• 关键词: Native Americans; clinical research; family genetics; gene expression; gene mutation; genetic disorder; human genetic material tag; human subject; linkage mapping; phenotype; protein C; protein deficiency; prothrombin; thrombosis

The objective of this project is to better understand the biosynthesis, activation, and functional properties of the vitamin K-dependent plasma proteins involved in blood clotting and the consequences of mutations in the proteins on hereditary thrombosis. This project specifically explores, through the study of protein C mutations, the fundamental mechanisms by which these proteins are modified, transported, and secreted prior to their involvement in Ca2+-membrane associated processes. Another direction of the project is the chromosomal localization and identification of a putative second gene, THROMC, that is associated with thrombotic disease in a large type I protein C deficient kindred of Native American decent. Specific aims are to identify new protein C mutations in families exhibiting thrombophilia; construct, express, and biochemically characterize secreted and non-secreted naturally occurring mutant forms of protein C; and determine by genetic linkage analysis and existence and location of a second gene (THROMC) associated with thrombosis. Family members are also phenotyped in regard to thrombotic disease and several clinical markers of the prothrombotic state, including protein C, prothrombin fragment 1.2, and fibrin D-dimer levels. Unrelated thrombophilic families with and without protein C deficiency are also examined for the association of THROMC with disease. During the reporting period 12/1/96-11/30/97, at the GCRC we obtained whole blood and plasma samples from 5 members of the protein C deficient kindred. Samples from 43 family members who live in other georgraphic locations were also obtained, but not at the GCRC. The total number of family members included in the sutdy is now 294. We will continue using the GCRC to obtain blood samples from family members living near here throughout the study period.

该项目的目的是更好地了解生物合成， 维生素K依赖性血浆的激活和功能特性 参与血液凝固的蛋白质以及 遗传性血栓形成的蛋白质 该项目具体 通过研究蛋白质C突变，探索了 这些蛋白质被修饰、转运和分泌的机制 在它们参与Ca 2+膜相关过程之前。 另一 该项目的方向是染色体定位， 鉴定推定的第二基因THROMC，其与 一个大的I型蛋白C缺陷型家族中的血栓性疾病 美国人的体面。 具体目标是确定新的蛋白C突变， 表现出血栓形成倾向的家族;构建、表达和生物化学 表征分泌型和非分泌型天然存在的突变体形式 蛋白质C;并通过遗传连锁分析确定和存在， 与血栓形成相关的第二个基因（THROMC）的位置。 家庭 成员还就血栓性疾病进行了表型分析， 血栓前状态的临床标志物，包括蛋白C， 凝血酶原片段1.2和纤维蛋白D-二聚体水平。 无关 有和没有蛋白C缺乏的血栓形成家族也是 检查THROMC与疾病的关系。 在本报告所 在1996年12月1日至1997年11月30日期间，我们在GCRC采集了全血和血浆 来自蛋白C缺乏家族的5名成员的样品。 样本 43名居住在其他地理位置的家庭成员也被 获得，但不是在GCRC。 家庭成员总数 目前，该报告中包含的数字为294。 我们会继续使用GCRC， 从住在附近的家庭成员那里获得血液样本， 学习期间。