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Keywords: Cardiovascular system; Targeted sequencing

T. Hsiao 1; Y.M. Chen 2; C.H. Lin 1; W.W. Lin 3

1) Department of Medical Research, Taichung Veterans General Hospital, Taichung City, Taiwan,; 2) Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taiwan.; 3) Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan

Background: Familial hypercholesterolemia (FH) is an autosomal dominant inheritable disease characterized with premature cardiovascular disease and high levels of low-density lipoprotein (LDL) despite intensive statin therapy. This study aimed to interrogate novel genetic variants of possible FH patients in Taiwan using a next-generation sequencing (NGS) platform.
Methods: We enrolled 89 possible FH participants (age 50.9 ± 13.8 years, 45 female, 44 male) with Dutch Lipid Clinic Network score 3-5. A customized targeted amplification panel of the coding region of LDLR, PCSK-9 and APOB genes were performed with the Illumina iSeq 100 platform.
Results: In total, we identified 14 pathogenic (12 LDLR, 2 APOB) and 6 likely pathogenic variants (5 LDLR, 1 APOB & LDLR). Three variant of unknown significance (VUS) were also categorized. The mean LDL levels were 137.6 ± 69.2 mg/dl after maximum dose of statin therapies. We found that LDL levels were significantly different among participants of pathogenic, likely pathogenic, benign or VUS groups (p = 0.045 by Kruskal-Wallis test).
Conclusions: NGS-based methods can be used to identify heterozygous FH patients of Chinese Han ancestry in the possible FH patients by Dutch Lipid Clinic Network score. However, subjects with VUS deserve further investigations.