Cholesterol Synthesis and Regulation

A 52-year-old man with a family history of premature coronary artery disease presents with xanthomas on his Achilles tendons and eyelids. Fasting lipid panel shows total cholesterol 480 mg/dL, LDL-C 420 mg/dL, and triglycerides 150 mg/dL. Clinical suspicion for familial hypercholesterolaemia is high. Which investigation would be most appropriate to confirm the diagnosis and assess the underlying genetic defect?

A 52-year-old man with familial hypercholesterolemia (FH) and a 48-year-old woman with polygenic hypercholesterolemia present to the lipid clinic. Both have elevated LDL cholesterol. Which feature best distinguishes FH from polygenic hypercholesterolemia?

A 48-year-old woman on atorvastatin 40 mg daily for hypercholesterolaemia reports muscle pain and weakness. Her serum creatine kinase (CK) is 2200 U/L (normal <200 U/L). Which investigation is most appropriate to determine whether statin-induced muscle toxicity is due to myopathy versus rhabdomyolysis?

Which regulatory mechanism is responsible for the decrease in HMG-CoA reductase expression when intracellular cholesterol levels are elevated?

A 52-year-old man with a family history of premature coronary artery disease presents with xanthomas on his Achilles tendons and eyelids. Serum total cholesterol is 580 mg/dL and LDL cholesterol is 420 mg/dL despite dietary modification. Which investigation is most appropriate to confirm the suspected diagnosis of familial hypercholesterolaemia?