Familial+hypercholesterolemia+(FH)

Familial hypercholesterolemia (FH) is a disease that disrupts the low-density lipoproteins (LDL) receptors on cell membranes. The cause of the disease is genetic and the disease disrupts the metabolism of lipoproteins. FH is directly related to a defective LDL receptor gene that is mapped to 19p13.1-13.3.1 More than 800 mutations have been found on this gene that cause FH.1 Since the gene is autosomal codominnant this means that a heterozygote parent probably passes the gene to half of their offspring and that the trait will be expressed due to its codominance.1 The defect in the LDL receptor gene effects all cells that have LDL receptors since the disease originates in the DNA therefore all transcription and then translation gives rise to a defective protein. The main organ that is influenced by the defect is the liver and this creates increased LDL in the plasma therefore it also effects the circulatory system.4 The firsts association of the symptoms and the genetic inheritance was expressed by a Norwegian Dr. C. Muller. He made the correlation that the high cholesterol levels of the patients seemed to correspond to an autosomal dominant inheritance pattern. Over 40 years later two doctors in Dallas, Dr. Joseph L. Goldstein and Dr. Michael S. Brown found the genetic cause for FH. They found the mechanism of FH to be the improper binding of LDL to its receptor to be the main cause for FH.2 Some claim the woman in the Mona Lisa painting have characteristics of the FH disease that can be seen under her right hand and on the left upper eyelid.3 Other than this painting there seems to be no "famous" people with the disease although there are a few reports in news papers or on news websites that have stories on people who have the disease. The major historical events that are linked with FH are just he discovery and advancement of treatments and mechanism for the disease. The symptoms for the disease are characterized clinically by "elevated levels of total and LDL cholesterol in the circulation, the presence of tendon xanthomas and premature atherosclerosis.4" The main symptom is the increase in the cholesterol in blood and this can create more problems including cardio vascular disease, and cardiac arrest. The increase in cholesterol also blocks the circulatory system making the heart work harder for the same result as an unaffected person. One main treatment of FH is to maintain a diet low in LDLs, this reduction of LDL intake means that the metabolism of the LDL is reduced and the buildup of LDL is contained. One study reported that treatment by atorvastatin (a drug, its a component of Lipitor) decreased tendon xanthomas, one of the symptoms of FH, in the Achilles tendon. Xanthomous is a depositing of lipids in tendons and connective tissue.5 These treatment options is the current research on the disease. Many studies are focusing on the effect of dieting on the disease, the results are found by analyzing LDL in plasma and studies like the xanthomous. Other research is still being done to identify the mutations of the LDL receptor gene. Further research is diving into the similarities between this disease and other similar disease where the LDL receptor works but is has a very low affinity to LDL. Figure 1: Flowchart of FH individual vs. individual without FH

1 Civeiria, Fernando. "Guidelines for the Diagnosis and Management of Heterozygous Familial Hypercholesterolemia." //Atherosclerosis// 173.1 (2004): 55-68. //Science Direct//. Web. 12 Dec. 2012. < [] >. (This was used because it had a good background discussion of the disease)
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2 "Familial Hypercholesterolemia." //Wikipedia//. Wikimedia Foundation, 12 June 2012. Web. 12 Dec. 2012.

3 Ose, Leiv. "The Real Code of Leonardo Da Vinci." //Current Cardiology Reviews// 4.1 (2008): 60-62. //NCBI//. Bentham Science Publishers. Web. 12 Dec. 2012.

4 Alonso, Rodrigo, Joep C. Defesche, Diego Tejedor, Sergio Castillo, Marianne Stef, Nelva Mata, Pilar Gomez-Enterria, Ceferino Martinez-Faedo, Lluis Forga, and Pedro Mata. "Genetic Diagnosis of Familial Hypercholesterolemia Using a DNA-array Based Platform." //Clinical Biochemistry// 42.9 (2009): 899-903. //Science Direct//. Web. 12 Dec. 2012. < [] >.

5 Tsouli, Sofia G., Vasilios Xydis, Maria I. Argyropoulou, Alexandros D. Tselepis, Moses Elisaf, and Dimitrios N. Kiortsis. "Regression of Achilles Tendon Thickness after Statin Treatment in Patients with Familial Hypercholesterolemia: An Ultrasonographic Study." //Atherosclerosis// 205.1 (2009): 151-55. //Science Direct//. Web. 12 Dec. 2012. < [] >.