Familial Hypercholesterolemia is a disease characterized by high levels of cholesterol in your body, specifically low-density lipoprotein (LDL). This "bad" type of cholesterol gets into your bloodstream and causes early cardiovascular diseases. More than 34 million American adults have elevated blood cholesterol levels, and the most common inherited form of it, Familial Hypercholesterolemia, occurs in 1 in every 500 people in most country on average, but is most common in populations including Afrikaners in South Africa, French Canadians, Lebanese, and Finns.
Normally, receptors on the surface of liver cells bind to and get rid of LDL (the "bad" cholesterol) from the bloodstream. The liver cells make cholesterol and keep the good type, keeping the body healthy and functional. In Familial hypercholesterolemia, these receptors are absent or reduced on the liver cells. Now, the LDL's binding capabilities to the liver cells are greatly reduced. Thus, the LDL stays in the body for longer as it is harder than high-density lipoproteins, or HDL (the "good" cholesterol) to be removed. The LDL can eventually build up in the bloodstream, forming fatty plaques on the blood vessels, called atherosclerosis. This can lead to many problems including high blood pressure and heart disease.
The most common genetic mutation causing FH, which is autosomal dominant, is in the LDL receptor, or LDLR, gene. This gene is located on the short arm of chromosome 19, and the protein product is 839 amino acids in length. The LDLR gene's activity is inversely related to LDL levels in blood. There are over 1000 different known mutations in the LDLR gene that cause familial hypercholesterolemia, resulting in 5 major classes of FH. Other less common mutations include those in the ApoB, PCSK9, and LDLRAP1 genes, and can cause FH through a variety of means, from reducing expression of LDLR on the liver cell surface to causing mutations in the lipoprotein particle that allows the LDL to bind to the receptor. The genetics of this disease allow it to propagate in families throughout generations.
Physical signs and symptoms of this disease include yellow deposits of cholesterol-rich fat in several body locations, and several heart risk factors, including heart attacks. This disease is a very real threat to individuals in our society because approximately 85% of individuals with FH have not been diagnosed and are not currently receiving treatment. Diagnosis occurs via mutation analysis or lipid measurements in the body. This disease is usually treated with drugs known as statins. These are a class of drugs that stimulate the liver to produce more LDL receptors to remove this cholesterol from the bloodstreams. These drugs are able to effectively lower the cholesterol levels in the bloodstream. However, these drugs are largely ineffective against the homozygous form of this disease, in which the receptors themselves are nonfunctional.
Familial hypercholesterolemia is a serious cardiovascular genetic disease that threatens many people worldwide. It can have severe implications for the afflicted, as blood cholesterol levels soar and cause other problems in the human body that can have a lasting detrimental effect. It is necessary that we step up as a society to face this prominent problem to try to find a universal solution for this disease, and treat those who suffer from it.
Bibliography
http://ghr.nlm.nih.gov/condition/hypercholesterolemia
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC161432/
http://www.jaoa.osteopathic.org/content/114/2/99.long
http://onlinelibrary.wiley.com/doi/10.1002/humu.1380010602/abstract;jsessionid=9FED5DAA799B67C8630F6413039D025A.f01t01
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)14234-1/fulltext