Phenotypic and Genetic Analyses of Korean Patients with Familial Hypercholesterolemia: Results from the KFH Registry 2020

被引：2

作者：

Kim, Hyoeun ^{[1
]}

Lee, Chan Joo ^{[2
]}

Kim, Sang-Hyun ^{[3
]}

Kim, Jang Young ^{[4
]}

Choi, Sung Hee ^{[5
]}

Kang, Hyun-Jae ^{[6
]}

Park, Kyong Soo ^{[6
]}

Cho, Byung Ryul ^{[7
]}

Kim, Byung Jin ^{[8
]}

Sung, Ki Chul ^{[8
]}

Jeong, In-Kyung ^{[9
]}

Jeong, Jin-Ok ^{[10
]}

Bae, Jang-Whan ^{[11
]}

Park, Jung Mi ^{[12
]}

Lee, Yunbeom ^{[13
]}

Jeong, Ilecheon ^{[13
]}

Han, Hyojun ^{[13
]}

Lee, Ji Hyun ^{[14
]}

Lee, Sang-Hak ^{[2
]}

机构：

[1] Yonsei Univ Hlth Syst, Dept Hlth Promot, Seoul, South Korea

[2] Yonsei Univ, Severance Hosp, Div Cardiol, Dept Internal Med,Coll Med, 134 Shinchon Dong, Seoul 120752, South Korea

[3] Seoul Natl Univ, Div Cardiol, Dept Internal Med, Boramae Med Ctr,Coll Med, Seoul, South Korea

[4] Yonsei Univ, Div Cardiol, Dept Internal Med, Wonju Coll Med, Wonju, South Korea

[5] Seoul Natl Univ, Dept Internal Med, Bundang Hosp, Coll Med, Seongnam, South Korea

[6] Seoul Natl Univ, Seoul Natl Univ Hosp, Dept Internal Med, Coll Med, Seoul, South Korea

[7] Kangwon Natl Univ, Sch Med, Div Cardiol, Dept Internal Med, Chunchon, South Korea

[8] Sungkyunkwan Univ, Kangbuk Samsung Hosp, Div Cardiol, Dept Internal Med,Sch Med, Seoul, South Korea

[9] Kyung Hee Univ, Dept Endocrinol & Metab, Kyung Hee Univ Hosp Gangdong, Sch Med, Seoul, South Korea

[10] Chungnam Natl Univ, Chungnam Natl Univ Hosp, Dept Internal Med, Cardiovasc Ctr,Sch Med, Daejeon, South Korea

[11] Chungbuk Natl Univ, Dept Internal Med, Coll Med, Cheongju, South Korea

[12] Yonsei Univ, Dept Biostat & Comp, Grad Sch, Seoul, South Korea

[13] Celemics Inc, Seoul, South Korea

[14] Kyung Hee Univ, Dept Clin Pharmacol & Therapeut, Sch Med, Seoul, South Korea

来源：

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS | 2022年 / 29卷 / 08期

关键词：

Diagnosis; Far East; Hyperlipoproteinemia type II; Mutation; CORONARY-ARTERY-DISEASE; LDL-RECEPTOR GENE; PATHOGENIC MUTATIONS; PREVALENCE; DIAGNOSIS; SPECTRUM; FH;

D O I：

10.5551/jat.63062

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

Aims: Familial hypercholesterolemia (FH) is currently a worldwide health issue. Understanding the characteristics of patients is important for proper diagnosis and treatment. This study aimed to analyze the phenotypic and genetic features, including threshold cholesterol levels, of Korean patients with FH. Methods: A total of 296 patients enrolled in the Korean FH registry were included, according to the following criteria: low-density lipoprotein-cholesterol (LDL-C) >190 mg/dL with tendon xanthoma or family history compatible with FH, or LDL-C >225 mg/dL. DNA sequences of three FH-associated genes were obtained using whole-exome or target exome sequencing. Threshold cholesterol levels for differentiating patients with FH/pathogenic variant (PV) carriers and predictors of PVs were identified. Results: Of the 296 patients, 104 had PVs and showed more obvious clinical findings, including higher cholesterol levels. PV rates ranged from 30% to 64% when patients were categorized by possible or definite type according to the Simon Broome criteria. Frequent PV types included missense variants and copy number variations (CNVs), while the most frequent location of PVs was p.P685L in LDLR. The threshold LDL-C levels for patient differentiation and PV prediction were 177 and 225 mg/dL, respectively. Younger age, tendon xanthoma, and higher LDL-C levels were identified as independent predictors of PVs, while traditional cardiovascular risk factors were predictors of coronary artery disease. Conclusions: Korean patients with FH had variable PV rates depending on diagnostic criteria and distinctive PV locations. The reported threshold LDL-C levels pave the way for efficient patient care in this population.

引用

页码：1176 / 1187

页数：12

共 25 条

[1] Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217 [J].