Cui Yuxia, Li Sufang, Zhang Feng, Song Junxian, Lee Chongyou, Wu Manyan, Chen Hong
Department of Cardiology, Peking University People's Hospital, Beijing, China.
Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China.
Clin Cardiol. 2019 Mar;42(3):385-390. doi: 10.1002/clc.23154. Epub 2019 Feb 19.
Familial hypercholesterolemia (FH) is a genetic cause of premature myocardial infarction (PMI). Early diagnosis of FH is critical for prognosis.
To investigate the prevalence of FH among a cohort of Chinese patients with PMI using genetic testing, and to evaluate different diagnostic criteria.
A total of 225 consecutive PMI patients were recruited. Low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin-kexin type 9 (PCSK9) and low-density lipoprotein receptor adaptor protein 1 (LDLRAP1) genes were detected by Sanger sequencing. FH was diagnosed using the Dutch Lipid Clinic Network (DLCN) criteria and modified DLCN criteria, respectively. The prevalence and clinical features of FH were analyzed.
In all PMI patients, pathogenic mutations of LDLR, APOB, PCSK9 and LDLRAP1 genes were found in 10 of 225 patients. Among all mutations, four mutations (LDLR c.129G>C, LDLR c.1867A>T, LDLRAP1 c.65G>C, and LDLRAP1 c.274G>A) were newly discovered. The prevalence of FH diagnosed by genetic testing was 4.4%. The prevalence of definite/probable FH diagnosed by DLCN and modified DLCN criteria reached 8.0% and 23.6%, respectively, and the mutation rates were 33.3% and 12.2%, respectively. The low-density lipo-protein cholesterol (LDL-C) levels in PMI patients with FH were far from goal attainment. Only one of the FH patients had LDL-C <2.5 mmol/L, and none of them had LDL-C <1.8 mmol/L.
The prevalence of FH among Chinese patients with PMI appeared relatively common. Underdiagnosis and undertreatment of FH are still a big problem, which should arouse a widespread concern.
家族性高胆固醇血症（FH）是早发性心肌梗死（PMI）的一个遗传病因。FH的早期诊断对预后至关重要。
采用基因检测调查一组中国PMI患者中FH的患病率，并评估不同的诊断标准。
共招募了225例连续的PMI患者。通过桑格测序检测低密度脂蛋白受体（LDLR）、载脂蛋白B（APOB）、前蛋白转化酶枯草溶菌素9型（PCSK9）和低密度脂蛋白受体衔接蛋白1（LDLRAP1）基因。分别使用荷兰脂质诊所网络（DLCN）标准和改良的DLCN标准诊断FH。分析FH的患病率和临床特征。
在所有PMI患者中，225例患者中有10例发现LDLR、APOB、PCSK9和LDLRAP1基因的致病突变。在所有突变中，新发现了4种突变（LDLR c.129G>C、LDLR c.1867A>T、LDLRAP1 c.65G>C和LDLRAP1 c.274G>A）。基因检测诊断的FH患病率为4.4%。根据DLCN和改良的DLCN标准诊断的确诊/可能FH患病率分别达到8.0%和23.6%，突变率分别为33.3%和12.2%。FH的PMI患者的低密度脂蛋白胆固醇（LDL-C）水平远未达到目标值。FH患者中只有1例LDL-C<2.5 mmol/L，且无一例LDL-C<1.8 mmol/L。
中国PMI患者中FH的患病率似乎相对较高。FH的诊断不足和治疗不足仍然是一个大问题，应引起广泛关注。
