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

随着分子生物学的进步，与 脂质/脂蛋白疾病[特别是动脉粥样硬化 心血管疾病（CVD）]最近已被确定， 表征了我们研究了载脂蛋白（a）基因及其 载脂蛋白（a）产品，用于改善患者的诊断， 为了更好地了解参与的致病事件， 心血管疾病的发展。允许进行综合研究 血清载脂蛋白（a）亚型的结构鉴定 (i.e.,重复的“kringle”单元的数量），而不是先前的 任意的异构体分配，没有普遍理解的 术语和许多不准确之处， 载脂蛋白（a）异构体大小与血清载脂蛋白（a）的相关性 浓度，我们发现的证据表明，异构体大小不是唯一的 决定血清载脂蛋白（a）水平的因子。那些缺乏任何 可检测的血清载脂蛋白（a）浓度（所谓的“无效”表型） 携带载脂蛋白（a）基因的两个等位基因。因此，结构 基因或其调控单位的变化， 该基因的表达可能是“无效”表型的原因。 载脂蛋白（a）基因和游离载脂蛋白（！）apo（a）蛋白 在无β脂蛋白血症患者的血清中检测到。进一步 研究是必要的，以更好地了解载脂蛋白（a）基因， 其有趣的产物，载脂蛋白（a），Lp（a）的独特成分， 粒子

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.