Predicting Low Density Lipoprotein-cholesterol Receptor Gene Mutations Using Lipid Profiles in Young Adults With Suspected Familial Hypercholesterolemia

Objective: Familial hypercholesterolemia (FH) is the most common autosomal dominant monogenic disorder and a significant contributor to premature cardiovascular disease. Despite its clinical importance, FH is frequently underdiagnosed, particularly in young adults with limited access to family history or follow-up. This study aimed to evaluate lipid profile-based predictors for low-density lipoprotein receptor (LDLR) gene mutations in young military personnel undergoing genetic testing for suspected FH.Method: We conducted a retrospective analysis of 111 individuals with clinical suspicion of familial hypercholesterolemia (FH) who underwent LDLR genetic testing between March 2022 and December 2023 at a Korean military hospital. Clinical parameters―including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and body mass index (BMI)―were compared based on mutation status. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine optimal cut-off values using the Youden index.Results : LDLR mutations were identified in 26 individuals (23.4%). The mutation-positive group had significantly higher LDL-C levels than the mutation-negative group (232.5 ± 58.8 vs. 197.6 ± 40.9 mg/dL, p = 0.008). The ROC analysis for LDL-C yielded an area under the curve (AUC) of 0.698, with an optimal threshold of 218.9 mg/dL (sensitivity 53.8%, specificity 85.9%). A multivariate model incorporating LDL-C, HDL-C, TG, and BMI improved the AUC to 0.711 (cut-off probability 0.29; sensitivity 53.8%, specificity 89.4%).Conclusion : An LDL-C threshold of 218.9 mg/dL may serve as a practical criterion for identifying candidates for LDLR gene testing among young adults with clinically suspected FH. A multivariate lipid-based approach may further improve the accuracy of FH screening, especially in military or resource-limited clinical settings.