ATP-binding cassette transporter A1 locus is not a major determinant of HDL-C levels in a population at high risk for coronary heart disease

• Published in: Atherosclerosis Vol. 166; no. 2; pp. 285 - 290
• Main Authors: Kakko, Sakari, Kelloniemi, Jani, von Rohr, Peter, Hoeschele, Ina, Tamminen, Minna, Brousseau, Margaret E., Kesäniemi, Y.Antero, Savolainen, Markku J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 01.02.2003; Elsevier
• Subjects: Adult; Analysis of Variance; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters - genetics; Biological and medical sciences; Cardiology. Vascular system; Case-Control Studies; Cholesterol, HDL - analysis; Cholesterol, HDL - metabolism; Coronary Disease - epidemiology; Coronary Disease - genetics; Coronary heart disease; Female; Finland - epidemiology; Genetic; Genetic polymorphisms; Genetic Predisposition to Disease; Genotype; Heart; High-density lipoproteins; Humans; Incidence; Male; Medical sciences; Middle Aged; Mutation; Phenotype; Probability; Quantitative trait locus; Risk Assessment; Sampling Studies; Sensitivity and Specificity; Genetic; Quantitative trait locus; High-density lipoproteins; Coronary heart disease; Genetic polymorphisms; Human; Cardiovascular disease; Genetic determinism; Quantitative trait loci; Cholesterol HDL; Risk factor; ABC transporter; Polymorphism
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/S0021-9150(02)00232-0

ATP-binding cassette transporter A1 (ABCA1) transports cellular cholesterol to lipid-poor apolipoproteins. Mutations in the ABCA1 gene are linked to rare phenotypes, familial hypoalphalipoproteinemia (FHA) and Tangier disease (TD), characterized by markedly decreased plasma high-density lipoprotein cholesterol (HDL-C) levels. The aim was to test if the ABCA1 locus is a major locus regulating HDL-C levels in the homogenous Finnish population with a high prevalence of coronary heart disease (CHD). Firstly, the ABCA1 locus was tested for linkage to HDL-C levels in 35 families with premature CHD and low HDL-C levels. Secondly, 62 men with low HDL-C levels and CHD were screened for the five mutations known to cause FHA. Thirdly, polymorphisms of the ABCA1 gene were tested for an association with HDL-C levels in a population sample of 515 subjects. The ABCA1 locus was not linked to HDL-C levels in the CHD families, and no carriers of the FHA mutations were found. The AA596 genotype was associated with higher HDL-C levels compared with the GG and GA genotypes in the women, but not in the men. The G596A genotypes explained 4% and the A2589G genotypes 3% of the variation in plasma HDL-C levels in women. The data suggest that the ABCA1 locus is of minor importance in the regulation of HDL-C in Finns.