Reference : Common genetic variation in ABCA1 is associated with altered lipoprotein levels and a...
Scientific journals : Article
Life sciences : Multidisciplinary, general & others
http://hdl.handle.net/10993/26996
Common genetic variation in ABCA1 is associated with altered lipoprotein levels and a modified risk for coronary artery disease
English
Clee, S. M. [> >]
Zwinderman, A. H. [> >]
Engert, J. C. [> >]
Zwarts, K. Y. [> >]
Molhuizen, H. O. [> >]
Roomp, Kirsten mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Jukema, J. W. [> >]
van Wijland, M. [> >]
van Dam, M. [> >]
Hudson, T. J. [> >]
Brooks-Wilson, A. [> >]
Genest Jr., J. [> >]
Kastelein, J. J. [> >]
Hayden, M. R. [> >]
2001
Circulation
Lippincott Williams & Wilkins
103
9
1198-1205
Yes (verified by ORBilu)
0009-7322
1524-4539
Hagerstown
MD
[en] ATP-Binding Cassette Transporters/ genetics ; Lipids/blood ; Lipoproteins/blood/ metabolism ; Middle Aged ; Phenotype ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Risk Factors ; Severity of Illness Index ; Survival Analysis ; Humans ; Genotype ; Genetic Variation ; Adult ; Age Factors ; Aged ; Amino Acid Substitution ; Body Mass Index ; Cholesterol, HDL/metabolism ; Cohort Studies ; Coronary Disease/ genetics/pathology ; Gene Frequency ; Triglycerides/blood
[en] BACKGROUND:

Low plasma HDL cholesterol (HDL-C) is associated with an increased risk of coronary artery disease (CAD). We recently identified the ATP-binding cassette transporter 1 (ABCA1) as the major gene underlying the HDL deficiency associated with reduced cholesterol efflux. Mutations within the ABCA1 gene are associated with decreased HDL-C, increased triglycerides, and an increased risk of CAD. However, the extent to which common variation within this gene influences plasma lipid levels and CAD in the general population is unknown.

METHODS AND RESULTS:

We examined the phenotypic effects of single nucleotide polymorphisms in the coding region of ABCA1. The R219K variant has a carrier frequency of 46% in Europeans. Carriers have a reduced severity of CAD, decreased focal (minimum obstruction diameter 1.81+/-0.35 versus 1.73+/-0.35 mm in noncarriers, P:=0.001) and diffuse atherosclerosis (mean segment diameter 2.77+/-0.37 versus 2.70+/-0.37 mm, P:=0.005), and fewer coronary events (50% versus 59%, P:=0.02). Atherosclerosis progresses more slowly in carriers of R219K than in noncarriers. Carriers have decreased triglyceride levels (1.42+/-0.49 versus 1.84+/-0.77 mmol/L, P:=0.001) and a trend toward increased HDL-C (0.91+/-0.22 versus 0.88+/-0.20 mmol/L, P:=0.12). Other single nucleotide polymorphisms in the coding region had milder effects on plasma lipids and atherosclerosis.

CONCLUSIONS:

These data suggest that common variation in ABCA1 significantly influences plasma lipid levels and the severity of CAD.
http://hdl.handle.net/10993/26996
10.1161/01.CIR.103.9.1198

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