Analysis of Gene mutation types and clinical characteristics of patients with familial hypercholesterolemia in Shijiazhuang

Objective This study aimed to investigate the incidence, types of gene mutations, and clinical characteristics of familial hypercholesterolemia (FH) in Shijiazhuang, while evaluating the effectiveness of targeted sequencing combined with high-risk population screening for FH. Methods A cross-sectional study was conducted involving 941 randomly selected normal individuals and 83 high-risk individuals. All participants underwent targeted sequencing for Low Density Lipoprotein Receptor (LDLR), Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9), and Apolipoprotein B (APOB). Logistic regression and ROC curves were used to analyze predictive factors for gene mutations. Results The mutation rate of LDLR in the general population is 0.318%, while the mutation rate of PCSK9 is 0.106%. In contrast, among high-risk groups, the LDLR mutation rate increases significantly to 18.072%, and the mutation rate of APOB is 1.204%. Predictive factors for carrying mutated genes were TG (odds ratio [OR] = 0.328, 95% confidence interval [CI] = 0.164–0.893, p = 0.026), incidence of fatty liver (OR = 0.274, 95%, CI = 0.081–0.924, p = 0.037), body mass index (BMI) (OR = 0.775, 95% CI = 0.637–0.944, p = 0.011), incidence of fatty corneal arch (OR = 3.375, 95% CI = 1.124–10.131, p = 0.030), DLCN score (OR = 2.075, 95% CI = 1.433–2.951, p < 0.050), respectively. The areas under the ROC curves of TG, DLCN scores, and BMI were 0.757 (cutoff value, 1.420), 0.854 (cutoff value, 5.500), and 0.734 (cutoff value, 24.950) respectively. Conclusions Targeted sequencing of LDLR, PCSK9, and APOB effectively identifies FH-related mutations, especially in high-risk populations, enhancing detection rates while reducing costs.