LDLR基因突变致纯合子家族性高胆固醇血症外周血单核细胞LDLR表达的研究

doi:10.3969/j.issn.1673-8640.2022.010.018

摘要/Abstract

摘要：

家族性高胆固醇血症（familial hypercholesterolemia，FH）是一种常染色体单基因显性遗传代谢性疾病，编码低密度脂蛋白受体（low-density lipoprotein receptor，LDLR）的LDLR基因是最常见的致病基因，LDLR基因突变可致细胞膜表面的LDLR缺失或功能异常，影响机体低密度脂蛋白（low-density lipoprotein，LDL）的代谢，导致胆固醇代谢障碍，最终使血清低密度脂蛋白胆固醇（low-density lipoprotein cholesterol，LDL-C）和总胆固醇（total cholesterol，TC）水平升高^[1-2]。根据基因型，FH可分为杂合型家族性高胆固醇血症（heterozygous familial hypercholesterolemia，HeFH）和纯合型家族性高胆固醇血症（homozygous familial hypercholesterolemia，HoFH）。HeFH携带1个致病等位基因，HoFH携带2个致病等位基因。HoFH较为罕见，患病率为1/100万~3/100万，HeFH患病率为0.20%~0.48%^[1]。我国人群FH患病率为0.18%^[2]。HoFH患儿的LDL-C水平是正常儿童的6~10倍，皮肤肌腱黄色瘤及早发冠心病（coronary heart disease，CHD）风险增加等是HoFH典型的临床特征；如未经治疗，HoFH患儿青少年期即可发生CHD，在30岁之前就可能因心肌梗死而死亡，甚至有发生猝死的风险^[3]。本研究拟分析1个FH家系LDLR基因突变及外周血单核细胞表面LDLR的表达情况。

张晰, 段明玥, 于壮, 魏孟姣, 张艳敏. LDLR基因突变致纯合子家族性高胆固醇血症外周血单核细胞LDLR表达的研究[J]. 检验医学, 2022, 37(10): 998-1001.

图/表 4

表1 先证者及其家系成员基因型和血脂水平、临床表型信息

家系成员	性别	年龄/岁	基因型	纯合/杂合	TC/ （mmol/L）	LDL-C/（mmol/L）	临床表型
先证者	男	8	LDLR E140K/LDLR E140K	纯合型	21.24^*	15.51^*	临床表型重，确诊时已出现心血管损伤
先证者父亲	男	44	LDLR E140K/+	杂合型	8.36^*	6.49^*	出现角膜环，双侧颈动脉硬化，有斑块形成
先证者母亲	女	41	LDLR E140K/+	杂合型	7.22^*	5.09^*	未发现
先证者大姨	女	43	+/+	野生型	4.66	4.11	未发现

图1 先证者及其家系成员单核细胞表面LDLR表达散点图注：（a）先证者；（b）先证者父亲；（c）先证者母亲；（d）先证者大姨。

图2 先证者及其家系成员单核细胞表面LDLR表达峰图注：（a）先证者；（b）先证者父亲；（c）先证者母亲；（d）先证者大姨。

图3 先证者及其家系成员单核细胞表面LDLR表达注：紫色为先证者，绿色为先证者父亲，蓝色为先证者母亲，粉色为先证者大姨。

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