Reference : ABCA1 regulatory variants influence coronary artery disease independent of effects on...
Scientific journals : Article
Life sciences : Multidisciplinary, general & others
ABCA1 regulatory variants influence coronary artery disease independent of effects on plasma lipid levels
Zwarts, K. Y. [> >]
Clee, S. M. [> >]
Zwinderman, A. H. [> >]
Engert, J. C. [> >]
Singaraja, R. [> >]
Loubser, O. [> >]
James, E. [> >]
Roomp, Kirsten mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Hudson, T. J. [> >]
Jukema, J. W. [> >]
Kastelein, J. J. [> >]
Hayden, M. R. [> >]
Clinical Genetics
Blackwell Publishing
Yes (verified by ORBilu)
United Kingdom
[en] 5' Untranslated Regions ; Random Allocation ; Promoter Regions, Genetic ; Polymorphism, Single Nucleotide ; Polymorphism, Restriction Fragment Length ; Phenotype ; Mutation ; Models, Genetic ; Male ; Lipids/ blood ; Humans ; Gene Expression Regulation ; Coronary Artery Disease/ genetics ; Cohort Studies ; ATP-Binding Cassette Transporters/ genetics ; Time Factors
[en] The authors have previously shown that individuals heterozygous for ABCA1 mutations have decreased high density lipoprotein cholesterol, increased triglycerides and an increased frequency of coronary artery disease (CAD), and that single nucleotide polymorphisms (SNPs) in the coding region of the ABCA1 gene significantly impact plasma lipid levels and the severity of CAD in the general population. They have now identified several SNPs in non-coding regions of ABCA1 which may be important for the appropriate regulation of ABCA1 expression (i.e. in the promoter, intron 1 and the 5′ untranslated region), and have examined the phenotypic effects of these SNPs in the REGRESS population. Out of 12 SNPs, four were associated with a clinical outcome. A threefold increase in coronary events with an increased family history of CAD was evident for the G-191C variant. Similarly, the C69T SNP was associated with a twofold increase in events. In contrast, the C-17G was associated with a decrease in coronary events and the InsG319 was associated with less atherosclerosis. For all these SNPs, the changes in atherosclerosis and CAD occurred without detectable changes in plasma lipid levels. These data suggest that common variation in non-coding regions of ABCA1 may significantly alter the severity of atherosclerosis, without necessarily influencing plasma lipid levels.

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