Effect of APOE ε4 allele on survival and fertility in an adverse environment.
Effect of APOE ε4 allele on survival and fertility in an adverse environment.
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DOI：
10.1371/journal.pone.0179497
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Westendorp RGJ
中科院分区：
文献类型：
--
作者：
van Exel E;Koopman JJE;Bodegom DV;Meij JJ;Knijff P;Ziem JB;Finch CE;Westendorp RGJ
载脂蛋白-ε4等位基因（APOE-ε4）与富裕人群的有害结果密切相关，包括动脉粥样硬化疾病，阿尔茨海默病和寿命缩短。尽管有这些不利的结果，APOE-ε4的人群频率很高。我们推测，APOE-ε4的高频率得以维持，是因为在进化过程中，当感染性病原体更普遍并且是死亡的主要原因时，APOE-ε4的有益作用。我们研究了一个加纳农村人口与高病原体暴露的选择性优势的APOE-ε4，生存和/或生育。这一加纳农村人口（n = 4 311）因广泛传播的传染病而死亡率很高，这些传染病是死亡的主要原因。我们通过暴露于高或低病原体水平分层后，研究了APOE-ε4是否与生存（总随访时间为30，262年）和生育力相关。从开放式威尔斯和河流取水的家庭被归类为暴露于高病原体水平，而低病原体暴露被归类为从钻孔威尔斯取水的家庭。我们发现了一个不显著但积极的生存益处，即每个APOE-ε4等位基因的风险比为0.80（95%置信区间：0.69至1.05），经性别、部落和社会经济地位调整。在40岁及以上的女性（n = 842）中，APOE-ε4与一生中的子女数量无关。然而，APOE-ε4与暴露于高病原体水平的女性的较高生育力相关。与不携带APOE-ε4等位基因的妇女相比，携带一个APOE-ε4等位基因的妇女平均多生一个孩子，携带两个APOE-ε4等位基因的妇女平均多生3.5个孩子（p = 0.018）。与富裕的现代人群相反，APOE-ε4在加纳农村人群中没有生存劣势。此外，APOE-ε4在高感染性环境中促进生育。我们的研究结果表明，APOE-ε4可能被认为是进化适应性。在富裕的现代人群中，APOE-ε4与迟发性衰老疾病的不良关联进一步表征了APOE-ε4作为拮抗多效性的一个例子。
The apolipoprotein-ε4 allele (APOE-ε4) is strongly associated with detrimental outcomes in affluent populations including atherosclerotic disease, Alzheimer’s disease, and reduced lifespan. Despite these detrimental outcomes, population frequencies of APOE-ε4 are high. We hypothesize that the high frequency of APOE-ε4 was maintained because of beneficial effects during evolution when infectious pathogens were more prevalent and a major cause of mortality. We examined a rural Ghanaian population with a high pathogen exposure for selective advantages of APOE-ε4, to survival and or fertility. This rural Ghanaian population (n = 4311) has high levels of mortality from widespread infectious diseases which are the main cause of death. We examined whether APOE-ε4 was associated with survival (total follow-up time was 30,262 years) and fertility after stratifying by exposure to high or low pathogen levels. Households drawing water from open wells and rivers were classified as exposed to high pathogen levels while low pathogen exposure was classified as those drawing water from borehole wells. We found a non-significant, but positive survival benefit, i.e. the hazard ratio per APOE-ε4 allele was 0.80 (95% confidence interval: 0.69 to 1.05), adjusted for sex, tribe, and socioeconomic status. Among women aged 40 years and older (n = 842), APOE-ε4 was not associated with the lifetime number of children. However, APOE-ε4 was associated with higher fertility in women exposed to high pathogen levels. Compared with women not carrying an APOE-ε4 allele, those carrying one APOE-ε4 allele had on average one more child and those carrying two APOE-ε4 alleles had 3.5 more children (p = 0.018). Contrary to affluent modern-day populations, APOE-ε4 did not carry a survival disadvantage in this rural Ghanaian population. Moreover, APOE-ε4 promotes fertility in highly infectious environments. Our findings suggest that APOE-ε4 may be considered as evolutionarily adaptive. Its adverse associations in affluent modern populations with later onset diseases of aging further characterize APOE-ε4 as an example of antagonistic pleiotropy.
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DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
影响因子：
3.6
作者：
May, Linda;Kuningas, Maris;Westendorp, Rudi G. J.
通讯作者：
Westendorp, Rudi G. J.
影响因子：
4
作者：
Corbo, RM;Ulizzi, L;De Stefano, GF
通讯作者：
De Stefano, GF
影响因子：
7.8
作者：
Kulminski AM;Culminskaya I;Ukraintseva SV;Arbeev KG;Arbeeva L;Wu D;Akushevich I;Land KC;Yashin AI
通讯作者：
Yashin AI
影响因子：
2.8
作者：
Boef, Anna G. C.;May, Linda;Eriksson, Ulrika K.
通讯作者：
Eriksson, Ulrika K.