Mutations in ABC1 in Tangier disease and familial high-density lipoproteindeficiency

Genes have a major role in the control of high-density lipoprotein (HDL) ch olesterol (HDL-C) levels. Here we have identified two Tangier disease (TD) families, confirmed 9q31 linkage and refined the disease locus to a limited genomic region containing the gene encoding the ATP-binding cassette trans porter (ABC1). Familiar HDL deficiency (FHA) is a more frequent cause of lo w HDL levels. On the basis of independent linkage and meiotic recombinants, we localized the FHA locus to the same genomic region as the TD locus, Mut ations in ABC1 were detected in both TD and FHA, indicating that TD and FHA are allelic. This indicates that the protein encoded by ABC1 is a key gate keeper influencing intracellular cholesterol transport, hence we have named it cholesterol efflux regulatory protein (CERP).