Genetics and Precision Medicine in Familial Hypercholesterolemia
Nicole Li
28/09/2026
Elevated levels of low-density lipoprotein cholesterol (LDL-C) define hypercholesterolemia, tying it closely to atherosclerosis and cardiovascular disease (CVD). While lifestyle factors such as diet and lack of exercise can play a major role, genetic determinants often shape how early symptoms appear, how intense they get, and how well treatments work. Familial hypercholesterolemia (FH) affects around 1 in every 250 individuals worldwide and is most commonly caused by mutations in low-density lipoprotein receptors (LDLR), apolipoprotein-B (APOB), or Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) proteins that impair LDL clearance. Due to this, cholesterol stays high from an early age, raising the chances of developing CVD much sooner than usual. Despite its prevalence, FH remains vastly underdiagnosed and undertreated, with over 90% of cases unidentified.
This narrative review summarizes the genetic basis of FH, evaluates how genotypes influence diagnosis and treatment, and assesses the current role of pharmacogenomics and personalized medicine in tailoring hypercholesterolemia management.
Furthermore, the paper evaluates the role of pharmacogenomics and personalized medicine frameworks in tailoring hypercholesterolemia management. By integrating genomic data with clinical and social factors, personalized medicine can improve adherence and help doctors choose the optimal treatment. Yet, ensuring fair implementation of genetic screening and precision therapies becomes a main concern, especially in areas where resources are thin. Moving forward means treating individuals, not averages, without leaving any community behind. Ultimately, advancing the genetic understanding of hypercholesterolemia may help complement standardized treatment approaches with increasingly individualized precision strategies for preventing cardiovascular outcomes.