Data from: Apolipoprotein (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 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 Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele?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.

那些对健康有害、尤其在老年时期危害更甚的等位基因（allele），被认为会在人群中持续留存，这是因为它们同时可通过拮抗多效性（antagonistic pleiotropy）为个体带来一定益处。载脂蛋白E（apolipoprotein E, ApoE）基因座上的ApoE4等位基因，会显著提升健康不良风险，但在诸多人群中仍以相对较高的频率存在。为何自然选择未将其替换为对健康有益的ApoE3等位基因？载脂蛋白E是合成卵巢雌激素与孕酮所需胆固醇前体的主要供应者，因此有研究提出，载脂蛋白E可能是导致生殖性能出现差异的潜在候选基因。我们的研究结果佐证了这一假说：对117名月经规律的女性进行分析后发现，携带至少一个ApoE4等位基因的受试者，其平均黄体孕酮水平为144.21 pmol·L⁻¹，显著高于未携带该等位基因的受试者（120.49 pmol·L⁻¹），这意味着前者具有更高的生育潜能。本次激素谱分析基于覆盖整个月经周期的每日检测数据。我们认为，携带ApoE4等位基因的女性孕酮水平更高这一发现，为解释人类种群中保留祖先型且会损害健康的ApoE4等位基因的进化机制提供了首个强有力的证据。