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

• Main Authors: Ye-Xuan Cao, Na-Qiong Wu, Di Sun, Hui-Hui Liu, Jing-Lu Jin, Sha Li, Yuan-Lin Guo, Cheng-Gang Zhu, Ying Gao, Qiu-Ting Dong, Geng Liu, Qian Dong, Jian-Jun Li
• Format: Article
• Language: English
• Published: BMC 2018-12-01
• Series: Journal of Translational Medicine
• Subjects: Familial hypercholesterolemia; Genetic testing; Very early-onset CAD
• Online Access: http://link.springer.com/article/10.1186/s12967-018-1737-7

Abstract Background Patients 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. Methods One 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. Results The 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. Conclusions FH 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.