Influence of the apolipoprotein E ε4 allele on human embryonic development

Zetterberg, Henrik; Palmér, Mona Seibt; Ricksten, Anne; Poirier, Judes; Palmqvist, Lars; Rymo, Lars; Zafiropoulos, Alexandros; Arvanitis, Demetrios A.; Spandidos, Demetrios Α.; Blennow, Kaj

doi:10.1016/s0304-3940(02)00198-2

Cited by 46 publications

(48 citation statements)

References 17 publications

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“…Numbers varied (from 118) due to missing observations. allele was also related to less frequently occurring spontaneous abortions, suggesting some protective effects during embryogenesis [68,69]. Our results provide support, although indirect, for the hypothesis that carriers of ApoE4 have a reproductive advantage.…”

Section: Discussionsupporting

confidence: 77%

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

et al. 2015

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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 Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele?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 21 ) than women with genotypes without ApoE4 (120.49 pmol l 21 ), 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.

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Section: Discussionsupporting

confidence: 77%

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

et al. 2015

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“…In the normal population, the ε4 allele is neuroprotective early in development, and has been associated with a decreased risk of spontaneous abortion (Zetterberg et al. 2002) and improved neurodevelopmental outcomes in infants with malnutrition (Oria et al. 2007, 2010) or lead exposure (Wright et al.…”

Section: Discussionmentioning

confidence: 99%

Organizational topology of brain and its relationship to ADHD in adolescents with d‐transposition of the great arteries

et al. 2016

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ObjectiveLittle is currently known about the impact of congenital heart disease (CHD) on the organization of large‐scale brain networks in relation to neurobehavioral outcome. We investigated whether CHD might impact ADHD symptoms via changes in brain structural network topology in a cohort of adolescents with d‐transposition of the great arteries (d‐TGA) repaired with the arterial switch operation in early infancy and referent subjects. We also explored whether these effects might be modified by apolipoprotein E (APOE) genotype, as the APOE ε2 allele has been associated with worse neurodevelopmental outcomes after repair of d‐TGA in infancy.MethodsWe applied graph analysis techniques to diffusion tensor imaging (DTI) data obtained from 47 d‐TGA adolescents and 29 healthy referents to construct measures of structural topology at the global and regional levels. We developed statistical mediation models revealing the respective contributions of d‐TGA, APOE genotype, and structural network topology on ADHD outcome as measured by the Connors ADHD/DSM‐IV Scales (CADS).ResultsChanges in overall network connectivity, integration, and segregation mediated worse ADHD outcomes in d‐TGA patients compared to healthy referents; these changes were predominantly in the left and right intrahemispheric regional subnetworks. Exploratory analysis revealed that network topology also mediated detrimental effects of the APOE ε4 allele but improved neurobehavioral outcomes for the APOE ε2 allele.ConclusionOur results suggest that disruption of organization of large‐scale networks may contribute to neurobehavioral dysfunction in adolescents with CHD and that this effect may interact with APOE genotype.

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“…(4) The polymerase chain reaction (PCR) analysis was used to identify genotypes by DNA. In addition, any studies which met the inclusion criteria, but where the samples came from fetal tissue material rather than maternal blood or provided no adequate information on the actual distribution of polymorphisms were excluded [21]. Review articles, case reports and case series were also not included.…”

Section: Search Criteriamentioning

confidence: 99%

“…With thorough evaluation, 431 studies were excluded for inappropriate research, contents that were either not relevant or did not investigate related genes with recurrent pregnancy loss, 16 were retrieved which described the association between the Apo E polymorphism and RPL, and finally, 6 were eligible for meta-analysis [15,17,19,20,23,24]. One of the studies was excluded because the samples were not maternal blood, the tissue used was fetal tissue material [21]; five were excluded because they were presented as a "letter to the editor", meaning that the contents were controversial regarding the association between recurrent pregnancy loss and apolipoprotein E [14,16,[25][26][27]; three were not included because they did not present detailed genotyping information [2,18,28]; and another study was excluded because it concentrated on patients with endometriosis [29]. The included studies were restricted to the English language.…”

Section: Characteristicsmentioning

confidence: 99%

Apolipoprotein E (Apo E) gene polymorphisms and recurrent pregnancy loss: a meta-analysis

Chen

et al. 2013

J Assist Reprod Genet

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Background Recently, a relationship between recurrent pregnancy loss (RPL) and Apolipoprotein E (Apo E) gene polymorphisms has been proposed. In order to investigate the real association between Apo E polymorphisms and RPL, our meta-analysis was carried out. Methods We estimated the association with RPL risk under dominant and recessive models, in combination with the OR and RR with a 95 % confidence interval (CI), which was used to assess the association between RPL and Apo E polymorphisms. Results According to our criterion, there were 6 studies included. The dominant model used the E4/E3 group and the OR was 1.919 (95 %CI: 1.016-3.625, I 2 =53.8 %), the RR was 1.308 (95 %Cl: 1.071-1.598) suggesting that carriers of the E4 allele would have a higher risk of causing spontaneous miscarriages. In addition, the OR was 0.727 (95 %CI: 0.566-0.932, I 2 =0.0 %) and RR was 0.923 (95 %CI: 0.867-0.982) in a fixed model for E3/E3 homozygotes versus other genotypes, suggesting that the Apo E3 polymorphism could be a protective factor. The OR was 1.365 (95 % CI: 1.029-1.811, I 2 =0 .0 %) in a fixed model comparing the E2 allele with the E3 allele, suggesting that Apo E2 polymorphisms may contribute to RPL as a risk factor. Furthermore, after conducting sensitivity analysis in the E4/E3 group, the results showed this to be consistent and the OR was 2.249 (95 %CI: 1.474-3.431). Conclusions There is a close association between RPL and Apo E gene polymorphisms. For RPL, the Apo E4 polymorphism could be a risk factor, the Apo E3 polymorphism may be a protective factor and the Apo E2 polymorphism may be another potential risk factor.

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Influence of the apolipoprotein E ε4 allele on human embryonic development

Cited by 46 publications

References 17 publications

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

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

Organizational topology of brain and its relationship to ADHD in adolescents with d‐transposition of the great arteries

Apolipoprotein E (Apo E) gene polymorphisms and recurrent pregnancy loss: a meta-analysis

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