(Circulation. 1995;91:265-269.)
© 1995 American Heart Association, Inc.
Articles |
Apolipoprotein E Polymorphism Predicts Death From Coronary Heart Disease in a Longitudinal Study of Elderly Finnish Men
From the National Public Health Institute (J.H.S., J.P., C.E.), Helsinki, Finland; Department of Human Genetics (J.H.S., K.E.Z., C.F.S.), University of Michigan (Ann Arbor); and Department of Community Health and General Practice (A.N.), University of Kuopio, Finland.
Correspondence to Dr Jari H. Stengård, National Public Health Institute, Department of Epidemiology and Health Promotion, Mannerheimintie 166, FIN-00300, Finland, Helsinki.
Background There is ample evidence from cross-sectional studies of an association between allelic variation of the gene coding for apolipoprotein E (apoE) and interindividual variation in plasma lipids, and the presence of coronary heart disease (CHD). There have been no prospective studies, however, to evaluate the usefulness of allelic variation of the apoE gene for predicting CHD.
Methods and Results Two samples of elderly Finnish men were
followed for 5 years, one in the east (n=297) and the other in the
southwest of Finland (n=369). At baseline, when the apoE genotypes were
assessed, the men were 65 to 84 years old. At the end of the follow-up,
the vital status of each man was determined, and cause of death was
coded. At baseline, relative frequencies of the three alleles–
2,
3, and 4–were 0.037, 0.827, and 0.136 in the eastern and
0.062,
0.763, and 0.175 in the southwestern samples, respectively
(
2=8.89, df=2, P<.012 for
difference between the samples). During the 5-year follow-up, a total
of 28 deaths from CHD were recorded in the eastern and 42 in the
southwestern sample. Relative CHD mortality was not heterogeneous
between the samples. Among those who died from CHD, there was a
doubling of the relative 4 allele frequency in both samples
(2=4.70, df=1, P<.03 for
the eastern sample; 2=7.11, df=1,
P<.01 for the southwestern sample).
Conclusions Allelic variation in the apoE gene is a statistically significant predictor of CHD death in these samples of elderly Finnish men.
Key Words: coronary disease • apolipoproteins • mortality
This article has been cited by other articles:
 |
|
 |
|
  K. Ding and I. J. Kullo Evolutionary Genetics of Coronary Heart Disease Circulation, January 27, 2009; 119(3): 459 - 467. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kolovou, D. Damaskos, K. Anagnostopoulou, and D. V. Cokkinos Apolipoprotein E Gene Polymorphism and Gender Ann. Clin. Lab. Sci., January 1, 2009; 39(2): 120 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F Zhang, M Lewis, G Yang, J Iriondo-Perez, Y Zeng, and J Liu Apolipoprotein E polymorphism, life stress and self-reported health among older adults J Epidemiol Community Health, April 1, 2008; 62(4): e3 - e3. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Ewbank Differences in the Association Between Apolipoprotein E Genotype and Mortality Across Populations J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2007; 62(8): 899 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. DeKroon, J. B. Robinette, A. B. Hjelmeland, E. Wiggins, M. Blackwell, M. Mihovilovic, M. Fujii, J. York, J. Hart, C. Kontos, et al. APOE4-VLDL Inhibits the HDL-Activated Phosphatidylinositol 3-Kinase/Akt Pathway via the Phosphoinositol Phosphatase SHIP2 Circ. Res., October 13, 2006; 99(8): 829 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Stengard, S. L. R. Kardia, S. C. Hamon, R. Frikke-Schmidt, A. Tybjaerg-Hansen, V. Salomaa, E. Boerwinkle, and C. F. Sing Contribution of regulatory and structural variations in APOE to predicting dyslipidemia J. Lipid Res., February 1, 2006; 47(2): 318 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. E. Swan, C. N. Lessov-Schlaggar, D. Carmelli, G. D. Schellenberg, and A. La Rue Apolipoprotein E {epsilon}4 and Change in Cognitive Functioning in Community-Dwelling Older Adults J Geriatr Psychiatry Neurol, December 1, 2005; 18(4): 196 - 201. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Scuteri, S. S. Najjar, D. Muller, R. Andres, C. H. Morrell, A. B. Zonderman, and E. G. Lakatta apoE4 allele and the natural history of cardiovascular risk factors Am J Physiol Endocrinol Metab, August 1, 2005; 289(2): E322 - E327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Pomara, L. Willoughby, K. Wesnes, D. J. Greenblatt, and J. J. Sidtis Apolipoprotein E {varepsilon}4 Allele and Lorazepam Effects on Memory in High-Functioning Older Adults Arch Gen Psychiatry, February 1, 2005; 62(2): 209 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Templeton, T. Maxwell, D. Posada, J. H. Stengard, E. Boerwinkle, and C. F. Sing Tree Scanning: A Method for Using Haplotype Trees in Phenotype/Genotype Association Studies Genetics, January 1, 2005; 169(1): 441 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. G Manton, X. Gu, H. Huang, and M. Kovtun Fuzzy set analyses of genetic determinants of health and disability status Statistical Methods in Medical Research, October 1, 2004; 13(5): 395 - 408. [Abstract] [PDF]
|
|
|
|
 |
|
 S. J Lewis and E. J Brunner Methodological problems in genetic association studies of longevity--the apolipoprotein E gene as an example Int. J. Epidemiol., October 1, 2004; 33(5): 962 - 970. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Mann, F. E. Thorngate, Y. Katoh-Fukui, H. Hamanaka, D. L. Williams, S. Fujita, and B. T. Lamb Independent effects of APOE on cholesterol metabolism and brain A{beta} levels in an Alzheimer disease mouse model Hum. Mol. Genet., September 1, 2004; 13(17): 1959 - 1968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification Endocr. Rev., August 1, 2004; 25(4): 629 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Song, M. J. Stampfer, and S. Liu Meta-Analysis: Apolipoprotein E Genotypes and Risk for Coronary Heart Disease Ann Intern Med, July 20, 2004; 141(2): 137 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Doherty, L. A. Fitzpatrick, A. Shaheen, T. B. Rajavashisth, and R. C. Detrano Genetic Determinants of Arterial Calcification Associated With Atherosclerosis Mayo Clin. Proc., February 1, 2004; 79(2): 197 - 210. [Abstract] [PDF]
|
|
|
|
 |
|
 G. D. Kolovou, D. Ch. Daskalova, M. Hatzivassiliou, N. Yiannakouris, N. D. Pilatis, M. Elisaf, D. P. Mikhailidis, M. A. Cariolou, and D. V. Cokkinos The Epsilon 2 and 4 Alleles of Apolipoprotein E and Ischemic Vascular Events in the Greek Population -- Implications for the Interpretation of Similar Studies Angiology, January 1, 2003; 54(1): 51 - 58. [Abstract] [PDF]
|
|
|
|
|
|
G. Kolovou, D. Daskalova, and D. P. Mikhailidis Apolipoprotein E Polymorphism and Atherosclerosis Angiology, January 1, 2003; 54(1): 59 - 71. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Lehtimaki, P. Dastidar, H. Jokela, T. Koivula, S. Lehtinen, C. Ehnholm, and R. Punnonen Effect of Long-Term Hormone Replacement Therapy on Atherosclerosis Progression in Postmenopausal Women Relates to Functional Apolipoprotein E Genotype J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4147 - 4153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Eichner, S. T. Dunn, G. Perveen, D. M. Thompson, K. E. Stewart, and B. C. Stroehla Apolipoprotein E Polymorphism and Cardiovascular Disease: A HuGE Review Am. J. Epidemiol., March 15, 2002; 155(6): 487 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.J.C. Slooter, M. L. Bots, L. M. Havekes, A. I. del Sol, M. Cruts, D. E. Grobbee, A. Hofman, C. Van Broeckhoven, J.C.M. Witteman, and C. M. van Duijn Apolipoprotein E and Carotid Artery Atherosclerosis: The Rotterdam Study Stroke, September 1, 2001; 32(9): 1947 - 1952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Klos, S. L. R. Kardia, R. E. Ferrell, S. T. Turner, E. Boerwinkle, and C. F. Sing Genome-Wide Linkage Analysis Reveals Evidence of Multiple Regions That Influence Variation in Plasma Lipid and Apolipoprotein Levels Associated With Risk of Coronary Heart Disease Arterioscler Thromb Vasc Biol, June 1, 2001; 21(6): 971 - 978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Batalla, R. Alvarez, J. R. Reguero, S. Hevia, G. Iglesias-Cubero, V. Alvarez, A. Cortina, P. Gonzalez, M. M. Celada, A. Medina, et al. Synergistic Effect between Apolipoprotein E and Angiotensinogen Gene Polymorphisms in the Risk for Early Myocardial Infarction Clin. Chem., December 1, 2000; 46(12): 1910 - 1915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Frikke-Schmidt, B. G. Nordestgaard, B. Agerholm-Larsen, P. Schnohr, and A. Tybjærg-Hansen Context-dependent and invariant associations between lipids, lipoproteins, and apolipoproteins and apolipoprotein E genotype J. Lipid Res., November 1, 2000; 41(11): 1812 - 1822. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. A. Nickerson, S. L. Taylor, S. M. Fullerton, K. M. Weiss, A. G. Clark, J. H. Stengård, V. Salomaa, E. Boerwinkle, and C. F. Sing Sequence Diversity and Large-Scale Typing of SNPs in the Human Apolipoprotein E Gene Genome Res., October 1, 2000; 10(10): 1532 - 1545. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. R. Isasi, S. Shea, R. J. Deckelbaum, S. C. Couch, T. J. Starc, J. D. Otvos, and L. Berglund Apolipoprotein epsilon 2 Allele Is Associated With an Anti-atherogenic Lipoprotein Profile in Children: The Columbia University BioMarkers Study Pediatrics, September 1, 2000; 106(3): 568 - 575. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. M. Olichney, L. A. Hansen, C. R. Hofstetter, J.-H. Lee, R. Katzman, and L. J. Thal Association Between Severe Cerebral Amyloid Angiopathy and Cerebrovascular Lesions in Alzheimer Disease Is Not a Spurious One Attributable to Apolipoprotein E4 Arch Neurol, June 1, 2000; 57(6): 869 - 874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. U. Gerdes, C. Gerdes, K. Kervinen, M. Savolainen, I. C. Klausen, P. S. Hansen, Y. A. Kesaniemi, and O. Fargeman The Apolipoprotein {epsilon}4 Allele Determines Prognosis and the Effect on Prognosis of Simvastatin in Survivors of Myocardial Infarction : A Substudy of the Scandinavian Simvastatin Survival Study Circulation, March 28, 2000; 101(12): 1366 - 1371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Dart and B. Cooper Independent Effects of Apo E Phenotype and Plasma Triglyceride on Lipoprotein Particle Sizes in the Fasting and Postprandial States Arterioscler Thromb Vasc Biol, October 1, 1999; 19(10): 2465 - 2473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. T. Bogardus Jr, J. Concato, and A. R. Feinstein Clinical Epidemiological Quality in Molecular Genetic Research: The Need for Methodological Standards JAMA, May 26, 1999; 281(20): 1919 - 1926. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. R. Kardia, M. B. Haviland, R. E. Ferrell, and C. F. Sing The Relationship Between Risk Factor Levels and Presence of Coronary Artery Calcification is Dependent on Apolipoprotein E Genotype Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 427 - 435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, D. A. Peterson, and D. Schubert Amyloid beta peptide alters intracellular vesicle trafficking and cholesterol homeostasis PNAS, October 27, 1998; 95(22): 13266 - 13271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. McCarron, K. W. Muir, C. J. Weir, A. G. Dyker, I. Bone, J.A.R. Nicoll, and K.R. Lees The Apolipoprotein E {epsilon}4 Allele and Outcome in Cerebrovascular Disease Stroke, September 1, 1998; 29(9): 1882 - 1887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Margaglione, D. Seripa, C. Gravina, E. Grandone, G. Vecchione, G. Cappucci, G. Merla, S. Papa, A. Postiglione, G. Di Minno, et al. Prevalence of Apolipoprotein E Alleles in Healthy Subjects and Survivors of Ischemic Stroke : An Italian Case-Control Study Stroke, February 1, 1998; 29(2): 399 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Pablos-Mendez, R. Mayeux, C. Ngai, S. Shea, and L. Berglund Association of Apo E Polymorphism With Plasma Lipid Levels in a Multiethnic Elderly Population Arterioscler Thromb Vasc Biol, December 1, 1997; 17(12): 3534 - 3541. [Abstract] [Full Text]
|
|
|
|
|
|
L. Ferrucci, J. M. Guralnik, M. Pahor, T. Harris, M.-C. Corti, M.-C. MHS, B. T. Hyman, R. B. Wallace, and R. J. Havlik Apolipoprotein E {epsilon}2 Allele and Risk of Stroke in the Older Population Stroke, December 1, 1997; 28(12): 2410 - 2416. [Abstract] [Full Text]
|
|
|
|
|
|
I. Raiha, J. Marniemi, P. Puukka, T. Toikka, C. Ehnholm, and L. Sourander Effect of Serum Lipids, Lipoproteins, and Apolipoproteins on Vascular and Nonvascular Mortality in the Elderly Arterioscler Thromb Vasc Biol, July 1, 1997; 17(7): 1224 - 1232. [Abstract] [Full Text]
|
|
|
|
|
|
P. W.F. Wilson, E. J. Schaefer, M. G. Larson, and J. M. Ordovas Apolipoprotein E Alleles and Risk of Coronary Disease: A Meta-analysis Arterioscler Thromb Vasc Biol, October 1, 1996; 16(10): 1250 - 1255. [Abstract] [Full Text]
|
|
|
|
|
|
J. G. Terry, G. Howard, M. Mercuri, M. G. Bond, and J. R. Crouse III Apolipoprotein E Polymorphism Is Associated With Segment-Specific Extracranial Carotid Artery Intima-Media Thickening Stroke, October 1, 1996; 27(10): 1755 - 1759. [Abstract] [Full Text]
|
|
|
|
 |
|
 L.-M. Dong and K. H. Weisgraber Human Apolipoprotein E4 Domain Interaction. ARGININE 61AND GLUTAMIC ACID 255INTERACT TO DIRECT THE PREFERENCE FOR VERY LOW DENSITY LIPOPROTEINS J. Biol. Chem., August 9, 1996; 271(32): 19053 - 19057. [Abstract] [Full Text] [PDF]
|
|