This Article Full Text Full Text (PDF) Supplemental Data Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Benn, M. Articles by Tybjærg-Hansen, A. Search for Related Content PubMed PubMed Citation Articles by Benn, M. Articles by Tybjærg-Hansen, A. Related Collections Lipid Cardiovascular Endocrinology

Polymorphisms in Apolipoprotein B and Risk of Ischemic Stroke

Department of Clinical Biochemistry (M.B., A.T.-H.), Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark; Department of Clinical Biochemistry (M.B., B.G.N.), Herlev University Hospital, DK-2730 Herlev, Denmark; The Copenhagen City Heart Study, Bispebjerg University Hospital (A.T.-H., B.G.N., J.S.J.), DK-2400 Copenhagen, Denmark; and Department of Cardiology (J.S.J.), Gentofte University Hospital, University of Copenhagen, DK-2900 Gentofte, Denmark

Address all correspondence and requests for reprints to: Anne Tybjærg-Hansen, M.D., D.M.Sc., Chief Physician and Associate Professor, Department of Clinical Biochemistry, KB3011, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. E-mail: at-h{at}rh.dk.

Context: Apolipoprotein B levels associate with risk of ischemic stroke. APOB polymorphisms may influence levels of apolipoprotein B and low-density lipoprotein (LDL), but whether they associate with risk of ischemic stroke is unknown.

Objective: We tested the hypothesis that the APOB T71I, A591V, P2712L, R3611Q, E4154K, and N4311S polymorphisms associate with risk of ischemic stroke in the general population and performed in vivo human LDL turnover studies of E4154K heterozygotes vs. K4154K homozygotes.

Design: This was a prospective study (the Copenhagen City Heart Study) with 23-yr, 100% complete follow-up.

Setting: The study was conducted with a Danish general population.

Participants: A total of 9157 women and men aged 20–80+ yr participated in the study.

Main Outcome Measures: Risk of ischemic cerebrovascular disease and ischemic stroke, apolipoprotein B and LDL levels, and LDL fractional catabolic rate were measured. The hypothesis was formulated before genotyping.

Results: APOB K4154K homozygotes had an age-adjusted hazard ratio of 0.4 (95% confidence interval 0.2–0.9) for ischemic cerebrovascular disease and 0.2 (0.1–0.7) for ischemic stroke relative to E4154E homozygotes. Corresponding multifactorially adjusted hazard ratios were 0.5 (0.2–1.0) and 0.2 (0.1–0.8). Furthermore, E4154K heterozygotes and K4154K homozygotes had lower levels of apolipoprotein B and LDL cholesterol, compared with E4154E homozygotes. Finally, E4154K heterozygotes had an increased fractional catabolic rate of LDL relative to E4154E homozygotes. None of the other polymorphisms studied influenced risk of ischemic stroke.

Conclusions: APOB K4154K homozygosity predicts a 3- to 5-fold reduction in risk of ischemic cerebrovascular disease and ischemic stroke. This may be explained by lower plasma levels of apolipoprotein B and LDL cholesterol caused by an increased catabolism of LDL particles, although another yet-unknown mechanism is also possible.

This article has been cited by other articles:

				J. H. Contois, J. P. McConnell, A. A. Sethi, G. Csako, S. Devaraj, D. M. Hoefner, and G. R. Warnick Apolipoprotein B and Cardiovascular Disease Risk: Position Statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices Clin. Chem., March 1, 2009; 55(3): 407 - 419. [Abstract] [Full Text] [PDF]