Question

10)Two types of cholesterol transport proteins, low-density lipoproteins (LDL) and high-density lipoproteins (HDL), bind to cholesterol and carry it through the bloodstream. Familial hypercholesterolemia (FH) is characterized by high cholesterol levels in the blood, which can lead to cardiovascular disease. FH is associated with a loss-of-function mutation of a gene that encodes LDL receptors in liver cells. Individuals who are heterozygous produce lower-than-normal amounts of the LDL receptors, and individuals who are homozygous for the mutant allele have no LDL receptor function. Individuals with FH can be treated with drugs that result in increased production of LDL receptors in liver cells. Which of the following best explains the observation that the drugs can effectively control blood cholesterol levels in individuals who are heterozygous but are not effective in individuals homozygous for the mutant allele?

A)The drugs repair the mutant allele by copying the wild-type allele.

b)The drugs prevent cholesterol from entering the liver cells in individuals who are heterozygous but not in individuals who are homozygous for the mutant allele.

c)Cholesterol molecules primarily bind to HDL receptors in individuals with FH.

d)There must be at least one copy of the wild-type LDL receptor allele to produce functional LDL receptors.

Answer 1

d)There must be at least one copy of the wild-type LDL receptor allele to produce functional LDL receptors.

Like many other genetic conditions, FH is inherited.  Each child of a person with FH has a 50% chance of inheriting the disorder so it is essential to screen parents, siblings and children of a person diagnosed with FH to find others who may have inherited the genes.

Mutations you inherit affects the type of FH one may have:

• One Inherited Mutation – Called Heterozygous Familial Hypercholesterolemia (HeFH), one abnormal mutation is passed down to a child, typically from one parent.
• Two Inherited Mutations - When the mutation for HeFH is passed on from both parents to their children this can result in Homozygous Familial Hypercholesterolemia (HoFH), the more rare and severe form of FH.

If Heterozygous FH, few LDL receptor protiens are still formed, but in Homozygous FH, both are mutated and hence no LDL receptor protiens are formed making it very severe.

Heterozygous FH is usually treated with statins. Statins act by inhibiting the enzyme hydroxymethylglutaryl CoA reductase (HMG-CoA-reductase) in the liver.

But, Homozygous FH is harder to treat. The LDL(low Density Lipoprotein) receptors are minimally functional, if at all. Only high doses of statins, often in combination with other medications, are modestly effective in improving lipid levels.[35] If medical therapy is not successful at reducing cholesterol levels, LDL apheresis may be used; this filters LDL from the bloodstream in a process reminiscent of dialysis.