The genetic disease familial Hypercholesterolemia that leads to an increase in blood cholesterol is caused due to
The genetic disease familial Hypercholesterolemia that leads to an increase in blood cholesterol is caused due to
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Correct Answer: Option B
Explanation
Familial Hypercholesterolaemia (FH): an autosomal dominant disorder of lipoprotein metabolism. Molecular basis: Loss-of-function mutations in the LDLR gene (LDL receptor, chromosome 19p13.2). Normal function: LDLR on hepatocytes and peripheral cells binds ApoB-100 on LDL particles → receptor-mediated endocytosis → LDL taken into cell → cholesterol released for cellular use → LDLR recycled to surface; excess intracellular cholesterol suppresses HMG-CoA reductase (reduces de novo synthesis) and downregulates LDLR expression. In FH: defective LDLR → LDL cannot be cleared from blood → plasma LDL-cholesterol dramatically elevated (>7 mmol/L in heterozygotes; >13 mmol/L in homozygotes) → premature atherosclerotic cardiovascular disease (ASCVD). PCSK9 is a regulatory protease that degrades LDLRs — anti-PCSK9 antibodies are now used therapeutically.