title: 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.
abstract: 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.
authors.affiliation: Department of Internal Medicine and Biocenter Oulu, University of Oulu, P.O. BOX 5000, 90014, Oulu, Finland. sakari.kakko@oulu.fi
authors.forename: Sakari
authors.initials: S
authors.lastname: Kakko
authors.forename: Jani
authors.initials: J
authors.lastname: Kelloniemi
authors.forename: Peter
authors.initials: P
authors.lastname: von Rohr
authors.forename: Ina
authors.initials: I
authors.lastname: Hoeschele
authors.forename: Minna
authors.initials: M
authors.lastname: Tamminen
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Brousseau
authors.forename: Y Antero
authors.initials: YA
authors.lastname: Kesäniemi
authors.forename: Markku J
authors.initials: MJ
authors.lastname: Savolainen
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000032:analysis / Q000378:metabolism*; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011336:Probability; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL