Scientists have searched intensively for the gene that causes this rare disorder because low levels of HDL are linked to coronary heart disease.
Cells make cholesterol as well as absorbing it from the blood plasma.
While cholesterol is needed for normal tissue function, an excessive build-up can lead to the formation of atherosclerotic plaques. To maintain the balance inside a cell, cholesterol is also transferred out of the cell and back into the plasma, where it is collected by HDL particles and transported to the liver. The cells of TD patients are unable to export cholesterol, leading to an accumulation of cholesterol in the tonsils and lymph glands, and in some cases, the arterial walls, where it can lead to severe arteriosclerosis. The discovery that mutations in ABC1 cause TD reveals that the protein encoded by ABC1 is needed for cholesterol efflux. As ABC1 mutations cause inherited defects in HDL metabolism, it is possible that subtle variations in ABC1 are responsible for the reduced levels of HDL observed in patients suffering coronary heart disease.