The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management.
The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management.
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DOI：
10.1016/s2213-8587(13)70191-8
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发表时间：
2014-08
影响因子：
44.5
通讯作者：
Wiklund, Olov
中科院分区：
文献类型：
--
作者：
Hegele, Robert A.;Ginsberg, Henry N.;Chapman, M. John;Nordestgaard, Borge G.;Kuivenhoven, Jan Albert;Averna, Maurizio;Boren, Jan;Bruckert, Eric;Catapano, Alberico L.;Descamps, Olivier S.;Hovingh, G. Kees;Humphries, Steve E.;Kovanen, Petri T.;Masana, Luis;Pajukanta, Paivi;Parhofer, Klaus G.;Raal, Frederick J.;Ray, Kausik K.;Santos, Raul D.;Stalenhoef, Anton F. H.;Stroes, Erik;Taskinen, Marja-Riitta;Tybjrg-Hansen, Anne;Watts, Gerald F.;Wiklund, Olov
血浆甘油三酯浓度是循环富含甘油三酯的脂蛋白及其代谢残余物的生物标志物。常见的轻度至中度高甘油三酯血症通常是多基因的，是由 30 多个基因中常见和罕见变异的累积负担造成的，通过遗传风险评分进行量化。罕见的常染色体隐性单基因高甘油三酯血症可由六个不同基因的大效应突变引起。非遗传因素会加剧高甘油三酯血症。根据最近的遗传数据，我们将这种疾病重新定义为两种状态：严重（甘油三酯浓度> 10 mmol/L），更有可能是单基因原因；轻度至中度（甘油三酯浓度 2-10 mmol/L）。由于易感等位基因的聚集和家庭中的次要因素，对家庭成员的生化筛查和咨询至关重要，但常规基因检测是不必要的。治疗包括生活方式和次要因素的管理以及药物治疗。对于严重的高甘油三酯血症，由于存在胰腺炎风险，因此需要进行干预；对于轻度至中度高甘油三酯血症，可以采取干预措施来预防心血管疾病，具体取决于甘油三酯浓度、伴随的脂蛋白紊乱和总体心血管风险。
Plasma triglyceride concentration is a biomarker for circulating triglyceride-rich lipoproteins and their metabolic remnants. Common mild-to-moderate hypertriglyceridaemia is typically multigenic, and results from the cumulative burden of common and rare variants in more than 30 genes, as quantified by genetic risk scores. Rare autosomal recessive monogenic hypertriglyceridaemia can result from large-effect mutations in six different genes. Hypertriglyceridaemia is exacerbated by non-genetic factors. On the basis of recent genetic data, we redefine the disorder into two states: severe (triglyceride concentration >10 mmol/L), which is more likely to have a monogenic cause; and mild-to-moderate (triglyceride concentration 2–10 mmol/L). Because of clustering of susceptibility alleles and secondary factors in families, biochemical screening and counselling for family members is essential, but routine genetic testing is not warranted. Treatment includes management of lifestyle and secondary factors, and pharmacotherapy. In severe hypertriglyceridaemia, intervention is indicated because of pancreatitis risk; in mild-to-moderate hypertriglyceridaemia, intervention can be indicated to prevent cardiovascular disease, dependent on triglyceride concentration, concomitant lipoprotein disturbances, and overall cardiovascular risk.