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Application of expanded genetic analysis in the diagnosis of familial hypercholesterolemia in patients with very early-onset coronary artery disease

Authors
  • Cao, Ye-Xuan
  • Wu, Na-Qiong
  • Sun, Di
  • Liu, Hui-Hui
  • Jin, Jing-Lu
  • Li, Sha
  • Guo, Yuan-Lin
  • Zhu, Cheng-Gang
  • Gao, Ying
  • Dong, Qiu-Ting
  • Liu, Geng
  • Dong, Qian
  • Li, Jian-Jun
Type
Published Article
Journal
Journal of Translational Medicine
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Dec 10, 2018
Volume
16
Issue
1
Identifiers
DOI: 10.1186/s12967-018-1737-7
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundPatients with monogenic familial hypercholesterolemia (FH) have high risk for coronary artery disease (CAD). A recent FH Expert Panel suggested that FH was underdiagnosed and undertreated which needs early diagnosis. Moreover, the proportion of DNA-confirmed FH patients hospitalized with very early-onset (≤ 35 years) CAD remains uncertain.MethodsOne hundred and five patients with age ≤ 35 years and LDL-C ≥ 3.4 mmol/L were tested for 9 genes (LDLR, APOB, PCSK9, APOE, STAP1, LIPA, LDLRAP1, ABCG5/8). Dutch Lipid Clinic Network (DLCN) and Simon Broome (SB) criteria for FH were also performed.ResultsThe prevalence of genetically confirmed FH was 38.1% (n = 40) in 105 patients. DLCN categorized 26.7% patients to probable and definite FH while SB identified 17.1% of patients with possible to definite FH. Twenty-five (62.5%) and seventeen (42.5%) patients with pathogenic mutations were undiagnosed according to SB and DLCN criteria. FH variant carriers, especially homozygotes, had significantly higher plasma LDL-C levels. The best LDL-C threshold for genetically confirmed FH was 4.56 mmol/L in the present study.ConclusionsFH is really a common cause for very young CAD patients (≤ 35 years) with a 38.1% of causative mutations in China and best LDL-C threshold for predicting mutations was 4.56 mmol/L. The underdiagnostic rate of clinical criteria was around 42.5–62.5%, suggesting that the expanded genetic testing could indeed promote the diagnosis of FH.

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