Can “deleterious genes variants” be beneficial? Antagonistic pleiotropy on the example of the ApoE gene

Paula Bartecka; Andrzej Galbarczyk

doi:10.5114/ms.2026.159848

eISSN: 2300-6722
ISSN: 1899-1874

Medical Studies/Studia Medyczne

Current issue Archive Manuscripts accepted About the journal Editorial board Abstracting and indexing Subscription Contact Ethical standards and procedures Supplements Instructions for authors Publication charge

Editorial System

Submit your Manuscript

Editorial Policies

Sarajevo Declaration on Integrity and Visibility of Scholarly Publications

Open access

1/2026
vol. 42

Send email

Copy url:

Review paper

Can “deleterious genes variants” be beneficial? Antagonistic pleiotropy on the example of the ApoE gene

Paula B. Bartecka

^{1, 2}

,

Andrzej Galbarczyk

²

Department of Environmental Health, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland
Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, Krakow, Poland

Medical Studies 2026; 42 (1): 26–31

DOI: https://doi.org/10.5114/ms.2026.159848

Online publish date: 2026/03/16

Article file

- Can deleterious.pdf [0.14 MB]

Get citation

PlumX metrics:

1. Buckland PR. Allele-specific gene expression differences in humans. Hum Mol Genet. 2004; 13(suppl_2): R255-R2–60.

2. Carter AJR, Nguyen AQ. Antagonistic pleiotropy as a widespread mechanism for the maintenance of polymorphic disease alleles. BMC Med Genet. 2011; 12: 160.

3. Medawar PB. Old age and natural death. Mod Quart. 1946; 2: 30-49.

4. Hamilton WD. The moulding of senescence by natural selection. J Theor Biol. 1966; 12(1): 12-45.

5. Williams GC. Pleiotropy, Natural Selection, and the Evolution of Senescence. Sci Aging Knowl Environ. 2001; 2001(1): cp13.

6. McMaster MW, Shah A, Kangarlu J, Cheikhali R, Frish- man WH, Aronow WS. The impact of the apolipoprotein E genotype on cardiovascular disease and cognitive disorders. Cardiol Rev. 2024; doi: 10.1097/CRD.0000000000000703.

7. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis. JAMA. 1997; 278(16): 1349-1356.

8. Niu W, Qi Y, Qian Y, Gao P, Zhu D. The relationship between apolipoprotein E e2/e3/e4 polymorphisms and hypertension: a meta-analysis of six studies comprising 1812 cases and 1762 controls. Hypertens Res. 2009; 32(12): 1060-1066.

9. Corbo RM, Ulizzi L, Piombo L, Scacchi R. Study on a possible effect of four longevity candidate genes (ACE, PON1, PPAR-, and APOE) on human fertility. Biogerontology. 2008; 9: 317-323.

10. Mahley RW. Central nervous system lipoproteins: ApoE and regulation of cholesterol metabolism. Arterioscler Thromb Vasc Biol. 2016; 36(7): 1305-1315.

11. Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis. 1988; 8(1): 1-21.

12. Wenham P, Price W, Blundell G. Apolipoprotein E genotyping by one-stage PCR. Lancet. 1991; i: 1158-1159.

13. Harerimana NV, Goate AM, Bowles KR. The influence of 17q21. 31 and APOE genetic ancestry on neurodegenerative disease risk. Front Aging Neurosci. 2022; 14: 1021918.

14. Mahley RW, Nathan BP, Pitas RE. Apolipoprotein E. Structure, function, and possible roles in Alzheimer’s disease. Ann N Y Acad Sci. 1996; 777(1): 139-145.

15. Fullerton SM, Clark AG, Weiss KM, Nickerson DA, Tay- lor SL, Stengård JH, Salomaa V, Vartiainen E, Perola M, Boerwinkle E, Sing CF. Apolipoprotein E variation at the sequence haplotype level: implications for the origin and maintenance of a major human polymorphism. Am J Hum Genet. 2000; 67(4): 881-900.

16. Kowalska A, Wiechmann I, Walter H. Genetic variability of apolipoprotein E in a Polish population. Hum Biol. 1998; 70: 1093-1099.

17. Bednarska-Makaruk M, Broda G, Kurjata P, Rodo M, Roszczynko M, Rywik S, Wehr H. Apolipoprotein E genotype, lipid levels and coronary heart disease in a Polish population group. Eur J Epidemiol. 2001; 17: 789-792.

18. Jasienska G, Ellison PT, Galbarczyk A, Jasienski M, Kalemba- Drozdz M, Kapiszewska M, Nenko I, Thune I, Ziomkiewicz A. Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy? Proc Biol Sci. 2015; 282(1803): 20142395.

19. Gamboa R, Hernandez-Pacheco G, Hesiquio R, Zuniga J, Masso F, Montaño LF, Ramos-Kuri M, Estrada J, Grana- dos J, Vargas-Alarcón G. Apolipoprotein E polymorphism in the Indian and Mestizo populations of Mexico. Hum Biol. 2000; 72: 975-981.

20. Corbo RM, Ulizzi L, Scacchi R, Martinez-Labarga C, De Stefano GF. Apolipoprotein E polymorphism and fertility: a study in pre-industrial populations. Mol Hum Reprod. 2004; 10(8): 617-620.

21. Sing CF, Davignon J. Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet. 1985; 37(2): 268.

22. Eichner JE, Dunn ST, Perveen G, Thompson DM, Stewart KE, Stroehla BC. Apolipoprotein E polymorphism and cardiovascular disease: a HuGE review. Am J Epidemiol. 2002; 155(6): 487-495.

23. Bennet AM, Di Angelantonio E, Ye Z, Wensley F, Dahlin A, Ahlbom A, Keavney B, Collins R, Wiman B, de Faire U, Danesh J. Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA. 2007; 298(11): 1300-1311.

24. Luo J, Yang H, Song BL. Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol. 2020; 21(4): 225-245.

25. Wilson PW, Schaefer EJ, Larson MG, Ordovas JM. Apolipoprotein E alleles and risk of coronary disease: a meta-analysis. Arterioscler Thromb Vasc Biol. 1996; 16: 1250-1255.

26. Davignon J, Cohn JS, Mabile L, Bernier L. Apolipoprotein E and atherosclerosis: insight from animal and human studies. Clin Chim Acta. 1999; 286(1–2): 115-143.

27. Song Y, Stampfer MJ, Liu S. Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease. Ann Intern Med. 2004; 141(2): 137-147.

28. Gerdes LU, Gerdes C, Hansen PS, Klausen IC, Færgeman O. Are men carrying the apolipoprotein 4-or 2 allele less fertile than 33 genotypes? Hum Genet. 1996; 98: 239-242.

29. Shi J, Liu Y, Liu Y, Li Y, Qiu S, Bai Y, Gu Y, Luo J, Cui H, Li Y, Zhao Q, Zhang K, Cheng Y. Association between ApoE polymorphism and hypertension: a meta-analysis of 28 studies including 5898 cases and 7518 controls. Gene. 2018; 675: 197-207.

30. Pirraglia E, Glodzik L, Shao Y. Lower mortality risk in APOE4 carriers with normal cognitive ageing. Sci Rep. 2023; 13(1): 15089.

31. Liu Y, Yu JT, Wang HF, Han PR, Tan CC, Wang C, Meng XF, Risacher SL, Saykin AJ, Tan L. APOE genotype and neuroimaging markers of Alzheimer’s disease: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2015; 86(2): 127-134.

32. Finch CE, Sapolsky RM. The evolution of Alzheimer disease, the reproductive schedule, and apoE isoforms. Neurobiol Aging. 1999; 20(4): 407-428.

33. Norwitz ER, Schust DJ, Fisher SJ. Implantation and the survival of early pregnancy. N Engl J Med. 2001; 345(19): 1400-1408.

34. Trumble BC, Charifson M, Kraft T, Garcia AR, Cummings DK, Hooper P, Lea AJ, Rodriguez DE, Koebele SV, Buetow K, Beheim B, Minocher R, Gutierrez M, Thomas GS, Gatz M, Stieglitz J, Finch CE, Kaplan H, Gurven M. Apolipoprotein- 4 is associated with higher fecundity in a natural fertility population. Sci Adv. 2023; 9(32): eade9797.

35. van Exel E, Koopman JJE, Bodegom D van, Meij JJ, Knijff P de, Ziem JB, Finch CE, Westendorp RGJ. Effect of APOE 4 allele on survival and fertility in an adverse environment. PLoS One. 2017; 12(7): e0179497.

36. Collazo MS, Porrata-Doria T, Flores I, Acevedo SF. Apolipoprotein E polymorphisms and spontaneous pregnancy loss in patients with endometriosis. Mol Hum Reprod. 2012; 18(7): 372-377.

37. Corbo RM, Scacchi R, Cresta M. Differential reproductive efficiency associated with common apolipoprotein e alleles in postreproductive-aged subjects. Fertil Steril. 2004; 81(1): 104-107.

38. Paoli D, Zedda S, Grassetti D, Gallo M, Corbo RM, Lombardo F, Lenzi A, Gandini L. Are apolipoprotein E alleles correlated with semen quality? Int J Androl. 2012; 35(5): 714-719.

39. Toniutto P, Fattovich G, Fabris C, Minisini R, Burlone M, Pravadelli C, Peraro L, Falleti E, Caldera F, Bitetto D, Pirisi M. Genetic polymorphism at the apolipoprotein E locus affects the outcome of chronic hepatitis B. J Med Virol. 2010; 82(2): 224-331.

40. Trumble BC, Stieglitz J, Blackwell AD, Allayee H, Beheim B, Finch CE, Gurven M, Kaplan H. Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden. FASEB J. 2017; 31(4): 1508.

41. Oria RB, Patrick PD, Oriá MOB, Lorntz B, Thompson MR, Azevedo OGR, Lobo RNB, Pinkerton RF, Guerrant RL, Lima AAM. ApoE polymorphisms and diarrheal outcomes in Brazilian shanty town children. Brazil J Med Biol Res. 2010; 43: 249-256.

42. Marchant NL, King SL, Tabet N, Rusted JM. Positive effects of cholinergic stimulation favor young APOE e4 carriers. Neuropsychopharmacology. 2010; 35(5): 1090-1096.

Copyright: © 2026 Jan Kochanowski University in Kielce This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

Can “deleterious genes variants” be beneficial? Antagonistic pleiotropy on the example of the ApoE gene

Paula B. Bartecka 1, 2 , Andrzej Galbarczyk 2

Paula B. Bartecka

^{1, 2}

,

Andrzej Galbarczyk

²