Effect of APOE ε4 allele on survival and fertility in an adverse environment
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Effect of APOE ε4 allele on survival and fertility in an adverse environment. / van Exel, Eric; Koopman, Jacob J. E.; Bodegom, David van; Meij, Johannes J.; Knijff, Peter de; Ziem, Juventus B.; Finch, Caleb E.; Westendorp, Rudi G J.
I: PLOS ONE, Bind 12, Nr. 7, e0179497, 06.07.2017, s. 1-13.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
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TY - JOUR
T1 - Effect of APOE ε4 allele on survival and fertility in an adverse environment
AU - van Exel, Eric
AU - Koopman, Jacob J. E.
AU - Bodegom, David van
AU - Meij, Johannes J.
AU - Knijff, Peter de
AU - Ziem, Juventus B.
AU - Finch, Caleb E.
AU - Westendorp, Rudi G J
PY - 2017/7/6
Y1 - 2017/7/6
N2 - BACKGROUND: 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.METHODS AND FINDINGS: 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).CONCLUSIONS: 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.
AB - BACKGROUND: 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.METHODS AND FINDINGS: 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).CONCLUSIONS: 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.
KW - Adult
KW - Aged
KW - Alleles
KW - Apolipoprotein E4
KW - Communicable Diseases
KW - Drinking Water
KW - Female
KW - Fertility
KW - Gene Expression
KW - Gene Frequency
KW - Ghana
KW - Humans
KW - Male
KW - Middle Aged
KW - Parity
KW - Pregnancy
KW - Prospective Studies
KW - Rural Population
KW - Social Class
KW - Survival Analysis
KW - Journal Article
U2 - 10.1371/journal.pone.0179497
DO - 10.1371/journal.pone.0179497
M3 - Journal article
C2 - 28683096
VL - 12
SP - 1
EP - 13
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 7
M1 - e0179497
ER -
ID: 185192675