SNP Shot: Genomic Insights

Familial hypercholesterolemia (FH) is a genetic condition leading to significantly elevated cholesterol levels in the bloodstream. Cholesterol, a wax-like substance vital for building cell membranes, producing hormones, and aiding fat digestion, is naturally produced by the body and also obtained from animal-derived foods like egg yolks, meat, poultry, fish, and dairy. In individuals with FH, the body struggles to eliminate excess cholesterol, resulting in its accumulation in the blood. This buildup significantly increases the risk of heart disease.

People with FH are at a high risk of developing coronary artery disease early in life. This occurs when surplus cholesterol deposits on the inner walls of blood vessels, especially the coronary arteries that supply blood to the heart. This abnormal cholesterol buildup forms plaques that narrow and harden the artery walls. As these plaques enlarge, they can obstruct the arteries and restrict blood flow to the heart. Plaque buildup in the coronary arteries can cause angina (chest pain) and dramatically increases the risk of a heart attack.

FH can also lead to health issues beyond the heart and blood vessels, due to cholesterol accumulation in other tissues. When cholesterol accumulates in tendons (tissues connecting muscles to bones), it causes distinctive growths called tendon xanthomas, most commonly affecting the Achilles tendons and tendons in the hands and fingers. Yellowish cholesterol deposits may also develop under the skin of the eyelids, known as xanthelasmata. Furthermore, cholesterol accumulation at the edge of the cornea (the clear front surface of the eye) can result in a gray ring called arcus cornealis.

Inheritance:

FH caused by mutations in the LDLR, APOB, or PCSK9 genes typically follows an autosomal dominant inheritance pattern. This means that inheriting just one copy of the mutated gene from either parent is enough to cause the condition. An affected individual usually inherits one mutated gene copy from an affected parent and one normal copy from the other parent. In rare cases, a person may inherit a mutated copy of the LDLR, APOB, or PCSK9 gene from both parents (meaning both parents have FH). This results in a more severe form of FH that often manifests in childhood. When FH is caused by mutations in the LDLRAP1 gene, it is inherited in an autosomal recessive pattern. This means that two copies of the mutated gene, one from each parent, are required for the condition to develop. The parents of an individual with autosomal recessive FH each carry one copy of the mutated gene, but typically have normal cholesterol levels themselves.