家族性高胆固醇血症早期心血管损害的多模态影像遗传学研究

Familial hypercholesterolemia (FH) is the most serious dominantly inherited disease of lipid metabolism disorders. A latest study reported the incidence rate of heterozygous FH was 1/ 200-1/500. And the major cause of death of FH was premature coronary heart disease.Some researchers believed that the causative mutation caused LDL metabolic disorders in FH patients, and increased cholesterol promoted atherosclerosis, triggering a series of cardiovascular disease. However, we found that the cardiovascular damage in homozygous FH patients was not proportional with LDL-C level using ultrasound. And different LDL-R mutations may lead to different degrees of cardiovascular damage. The latest study also found that LPA gene polymorphism site was significantly associated with the progress of aortic stenosis. In this study, we will study the cardiovascular damage of FH patients using the multimodal Imaging technology combining with ultrasound,nuclear medicine imaging and genetics, in order to determine if the gene mutation of LDL and LPA leading to cholesterol metabolic disorders and increasing the sensitivity of LDL-C in cardiovascular system,leading to early cardiovascular damage in FH patients. Our study will help early assessing the cardiovascular damage of FH patients and providing targets for early intervention.

家族性高胆固醇血症（familial hypercholesterlolemia，FH）是脂质代谢疾病中最严重的一种显性遗传性疾病，最新报道FH杂合子发病率高达1/200-1/500，早发冠心病是FH致死的主要原因。以往认为致病基因突变导致FH患者LDL代谢紊乱，通过胆固醇明显升高促进动脉粥样硬化，引发一系列心血管病变。但是，我们应用超声发现FH纯合患者心血管损害与LDL-C水平不成正比，LDL-R突变位点不同可能导致心血管损伤严重程度不同，最新研究也发现LPA基因一个多态位点与主动脉狭窄进展显著相关。本研究应用超声和核素多模态影像技术结合基因遗传学评估FH患者心血管损害，明确LDL联合LPA基因变异一方面引起胆固醇代谢紊乱，一方面引起心血管系统对LDL-C敏感性增强，最终导致FH患者早期心血管损害，将有助于早期评估FH患者心血管疾病演变规律，为早期干预治疗提供靶点。

家族性高胆固醇血症（familial hypercholesterlolemia，FH）是脂质代谢疾病中最严重的一种显性遗传性疾病，最新报道FH杂合子发病率高达1/200-1/500，早发冠心病是FH致死的主要原因。筛查并收集FH纯合子及杂合子患者，对FH患者进行问卷调查、生化检查、采集血样本。对筛查出的FH患者及其家系行常规超声心动图、ATP负荷超声冠脉血流储备检查，应用斑点追踪成像技术分析患者心脏及血管结构及功能早期变化的超声参数，建立超声数据库。利用靶向捕获重测序筛选FH家系LDL-C相关基因突变，并根据测序结果，进行实验分组并建立数据库。我们建立了汉族家族性高胆固醇血症患者遗传与影像学的队列研究，并采用经胸多普勒冠脉血流成像技术无创性评价冠状动脉血流。