Apolipoprotein Isoform E4 Does Not Increase Coronary Heart Disease Risk in Carriers of Low-Density Lipoprotein Receptor Mutations

• DOI: 10.1161/circgenetics.111.959858
• Publication Date: 2011-10-19T03:46:23Z
• Authors: Jorie Versmissen; Daniëlla M. Ooste...; Menno Hoekstra; Ruud Out; Jimmy F.P. Berbée; Adriana C. Blomme...; Leonie van Vark-v...; Ranitha Vongpromek; Tim Vanmierlo; Joep C. Defesche; Monique Mulder; John J.P. Kastelein; Eric J.G. Sijbrands
• Keywords: Adult; Male; 0301 basic medicine; Heterozygote; familial hypercholesterolemia; Apolipoprotein E4; Coronary Artery Disease; Middle Aged; 3. Good health; Cohort Studies; Hyperlipoproteinemia Type II; 03 medical and health sciences; SDG 3 - Good Health and Well-being; Receptors, LDL; Risk Factors; Mutation; Humans; Female; coronary heart disease; apolipoprotein E; EMC COEUR-09; Aged

Background— In humans, the E4 allele of apolipoprotein E gene is associated with increased coronary heart disease risk. Surprisingly, in rodents, only accelerates atherosclerotic process when transgenic for human low-density lipoprotein receptor (LDLR) protein. We therefore investigated whether LDLR locus interacted genotype on risk patients clinically diagnosed familial hypercholesterolemia and without mutation. presence an mutation diminishing function was protective E4/E4 carriers. Methods Results— a cohort 2400 hypercholesterolemia, we found 1383 patients, whereas 1013 such not present. 92 homozygous , conferred lower (hazard ratio, 0.16; 95% CI, 0.05–0.58; P =0.005). Mirroring these results, also 0.26; hazard 0.08–0.80; =0.02). Conclusions— key to detrimental effects humans. Kinetic studies humans are now required study consequences our observation prevention both Alzheimer disease.