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Proc Biol Sci. 2015 Mar 22;282(1803):20142395. doi: 10.1098/rspb.2014.2395.

Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?

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Department of Environmental Health, Jagiellonian University Medical College, Krakow, Poland
Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
Department of Environmental Health, Jagiellonian University Medical College, Krakow, Poland.
Center for Innovatics, Nowy Sacz Business School-National-Louis University, Zielona 27, 33-300 Nowy Sacz, Poland.
Andrzej Frycz Modrzewski Krakow University, Krakow, Poland.
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway The Cancer Center, Oslo University Hospital, Oslo, Norway.
Polish Academy of Sciences, Unit of Anthropology in Wroclaw, Poland.


The alleles that are detrimental to health, especially in older age, are thought to persist in populations because they also confer some benefits for individuals (through antagonistic pleiotropy). The ApoE4 allele at the ApoE locus, encoding apolipoprotein E (ApoE), significantly increases risk of poor health, and yet it is present in many populations at relatively high frequencies. Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele? ApoE is a major supplier of cholesterol precursor for the production of ovarian oestrogen and progesterone, thus ApoE has been suggested as the potential candidate gene that may cause variation in reproductive performance. Our results support this hypothesis showing that in 117 regularly menstruating women those with genotypes with at least one ApoE4 allele had significantly higher levels of mean luteal progesterone (144.21 pmol l(-1)) than women with genotypes without ApoE4 (120.49 pmol l(-1)), which indicates higher potential fertility. The hormonal profiles were based on daily data for entire menstrual cycles. We suggest that the finding of higher progesterone in women with ApoE4 allele could provide first strong evidence for an evolutionary mechanism of maintaining the ancestral and health-worsening ApoE4 allele in human populations.


ApoE; antagonistic pleiotropy; apolipoprotein polymorphism; fertility; progesterone

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