TECHNIQUES FOR THE DETERMINATION OF GENES INVOLVED IN LIPID/LIPOPROTEIN DISORDERS

脂质/脂蛋白紊乱相关基因的测定技术

• 批准号: 3752265
• 负责人: G CSAKO
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3752265
• 关键词: abetalipoproteinemias; alleles; atherosclerosis; blood lipid; cardiovascular disorder diagnosis; gene expression; genetic disorder diagnosis; genetic techniques; lipoprotein disorder; molecular pathology; protein isoforms; structural genes

With advancements in molecular biology, genes associated with lipid/lipoprotein disorders [in particular, atherosclerotic cardiovascular disease, (CVD)] have been recently identified and characterized. We studied the gene for apolipoprotein(a) and its product, apolipoprotein (a), for improved diagnosis of patients and for better understanding of pathogenic events involved in the development of cardiovascular disease. Comprehensive studies allowed the identification of serum apo(a) isoforms in terms of structure (i.e., the number of repeat "kringle" units), as opposed to earlier arbitrary isoform assignments with no universally understandable nomenclature and numerous inaccuracies Despite a generally inverse correlation between apo(a) isoform size and serum apo(a) concentration, we found evidence that isoform size is not the only factor that determines serum apo(a) levels. individuals who lack any detectable serum apo(a) concentration (the so-called "null" phenotype) were found to carry two alleles of the apo(a) gene. Thus, structural changes in the gene or in its regulatory unit(s) that prevent expression of the gene may be responsible for the "null" phenotype. Two alleles of the apo(a) gene and free (!) apo(a) protein were detected in the serum of a patient with abetalipoproteinemia. Further studies are necessary to better understanding of the apo(a) gene and its intriguing product, apo(a), the unique component of the Lp(a) particle.

随着分子生物学的进步，与相关的基因 脂质/脂蛋白疾病[特别是动脉粥样硬化 心血管疾病（CVD）]最近已被识别并且 特点。我们研究了载脂蛋白（a）基因及其 产品载脂蛋白 (a)，用于改善患者的诊断和 为了更好地了解参与的致病事件 心血管疾病的发展。允许综合研究 血清 apo(a) 亚型的结构鉴定 （即重复“kringle”单元的数量），与之前的相反 没有普遍理解的任意异构体分配 尽管普遍相反，但命名法和许多不准确之处 apo(a) 异构体大小与血清 apo(a) 之间的相关性 浓度，我们发现证据表明异构体大小并不是唯一的 决定血清apo(a)水平的因素。缺乏任何 可检测的血清 apo(a) 浓度（所谓的“无效”表型） 被发现携带 apo(a) 基因的两个等位基因。因此，结构 基因或其调控单元的变化阻止 该基因的表达可能是造成“无效”表型的原因。 apo(a) 基因和游离 (!) apo(a) 蛋白的两个等位基因是 在无β脂蛋白血症患者的血清中检测到。更远 为了更好地了解 apo(a) 基因和 其有趣的产品，apo(a)，Lp(a) 的独特成分 粒子。