ABCA1(Alabama): a novel variant associated with HDL deficiency and premature coronary artery disease.
The ATP-binding cassette transporter, ABCA1, is a member of the ABC superfamily of proteins involved in the active transport of substrates across cellular membranes. Recent studies have implicated mutations in ABCA1 as the cause of Tangier disease (TD) and familial hypoalphalipoproteinemia (FHA). To evaluate the molecular basis of low high density lipoprotein (HDL) in a family with premature coronary artery disease, single strand conformational polymorphism analysis was performed for all coding regions and splice site junctions of ABCA1 with the genomic DNA of the proband. The proband and affected individuals were heterozygotes for C254T with proline converted to leucine (P85L). This mutation was not identified in over 400 chromosomes of healthy subjects. In the FHA kindred, family members heterozygous for the ABCA1 variant also exhibited corresponding low levels of HDL cholesterol. These data confirm recent data that a single defective allele in ABCA1 may be associated with reduced HDL cholesterol and FHA.
Section of Cardiology, Department of Medicine, University of Maryland and Veterans Administration Medical Center, 22 S. Greene St., S3B06, Baltimore, MD 21201, USA.
Seung Ho
SH
Hong
Jeffrey
J
Rhyne
Karen
K
Zeller
Michael
M
Miller
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D001483:Base Sequence; D008076:Cholesterol, HDL / Q000097:blood / Q000172:deficiency*; D003131:Combined Modality Therapy; D001026:Coronary Artery Bypass / Q000379:methods; D003324:Coronary Artery Disease / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D013631:Tangier Disease / Q000150:complications / Q000175:diagnosis*
D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL