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

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 p...

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Published in:Proceedings of the Royal Society. B, Biological sciences Biological sciences, 2015-03, Vol.282 (1803), p.20142395-20142395
Main Authors: Jasienska, Grazyna, Ellison, Peter T., Galbarczyk, Andrzej, Jasienski, Michal, Kalemba-Drozdz, Malgorzata, Kapiszewska, Maria, Nenko, Ilona, Thune, Inger, Ziomkiewicz, Anna
Format: Article
Language:English
Subjects:
Adult
Alleles
Antagonistic Pleiotropy
Apoe
Apolipoprotein E3 - genetics
Apolipoprotein E4 - genetics
Apolipoprotein Polymorphism
Female
Fertility
Fertility - genetics
Genetic Pleiotropy
Humans
Menstrual Cycle
Polymorphism, Genetic
Progesterone
Progesterone - analysis
Reproduction - genetics
Saliva - chemistry
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Summary: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 Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele?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.
ISSN:0962-8452
1471-2954
DOI:10.1098/rspb.2014.2395