Cholesterol is synthesized in the HMG-CoA reductase pathway. LDL cholesterol normally circulates in the body for 2.5 days, and subsequently the apolipoprotein B portion of LDL cholesterol binds to the LDL receptor on the liver cells, triggering its uptake and digestion. This process results in the removal of LDL from the circulatory system. Synthesis of cholesterol by the liver is suppressed in the HMG-CoA reductase pathway. In<unk> , LDL receptor function is reduced or absent, and LDL circulates for an average duration of 4.5 days, resulting in significantly increased level of LDL cholesterol in the blood with normal levels of other lipoproteins. In mutations of ApoB, reduced binding of LDL particles to the receptor causes the increased level of LDL cholesterol. It is not known how the mutation causes LDL receptor dysfunction in mutations of PCSK9 and ARH. Although atherosclerosis occurs to a certain degree in all people, people with<unk>  may develop accelerated atherosclerosis due to the excess level of LDL. The degree of atherosclerosis approximately depends on the number of LDL receptors still expressed and the functionality of these receptors. In many heterozygous forms of<unk> , the receptor function is only mildly impaired, and LDL levels will remain relatively low. In the more serious homozygous forms, the receptor is not expressed at all. Some studies of<unk>  cohorts suggest that additional risk factors are generally at play when a person develops atherosclerosis. In addition to the classic risk factors such as smoking, high blood pressure, and diabetes, genetic studies have shown that a common abnormality in the prothrombin gene (G20210A) increases the risk of cardiovascular events in people with<unk> . Several studies found that a high level of lipoprotein(a) was an additional risk factor for ischemic heart disease. The risk was also found to be higher in people with a specific genotype of the angiotensin-converting enzyme (ACE).
Familial hypercholesterolemia
Familial hypertriglyceridemia
Combined hyperlipidemia
Apolipoprotein B deficiency
Familial multiple lipomatosis
Marfanoid
Fruitarianism
Fabry disease