Familial hypercholesterolemia results from mutations in the LDL receptor gene, causing plasma LDL cholesterol to increase because it is not catabolized or taken up by the liver. It is an autosomal dominant disorder with a carrier rate of 1 in 500, so the frequency of homozygosity is 1 in 1 million. Heterozygotes have total serum cholesterol levels twice normal; homozygotes have levels even higher, with death from myocardial infarction by the second decade. The statin drugs inhibit the HMG-CoA reductase and reduce cholesterol levels in heterozygotes. Steroid hormone receptors, such as those for cortisol, are located in the cell nucleus. Insulin receptors play a role in glucose metabolism and glycemic control that may be part of diabetes mellitus with risk for atherosclerosis; statin drugs have no effect on diabetes mellitus. Abnormal leptin receptors may play a role in some forms of obesity. TGF-a is a growth factor with a role in inflammation, cell proliferation, and repair.