ApoE genotypes are associated with age at natural menopause in Chinese females

Meng, Fantao; Wang, Yanli; Liu, Ji; Zhao, Jun; Liu, Rong‐Yu; Zhou, Jiang‐Ning

doi:10.1007/s11357-011-9287-4

Cited by 15 publications

(10 citation statements)

References 46 publications

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“…Recently, several groups have reported the possible positive function of ApoE4 in young carriers [23–26]. We also found that ApoE4 was associated with longer reproductive period in Chinese females [27]. These evidences indicated that ApoE4 may play different role in young and elderly carriers.…”

Section: Discussionsupporting

confidence: 52%

Apolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells

Liu¹,

Meng²,

Wang

et al. 2012

Journal of Pineal Research

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Previous studies have demonstrated that apolipoprotein E (ApoE) genotype and melatonin are closely associated with Alzheimer's disease (AD). However, the relationship between ApoE genotype and melatonin remains unclear. Recently, we reported that cultured rat cortical astrocytes and glioma C6 cells synthesize melatonin. In the current study, we investigated the effect of ApoE genotype on melatonin biosynthesis. C6 cells with stable expression of ApoE isoforms (ApoE 2, 3 and 4) were established. A higher level of melatonin was demonstrated in cultured ApoE4-C6 cells than that in ApoE3-C6 cells. In addition, we found that N-acetyltransferase (NAT) protein level was up-regulated in ApoE4-C6 cells compared with ApoE3-C6 cells. Further study suggested that mRNA expression of monoamine oxidase A (MAOA) and monoamine oxidase B (MAOB) decreased in ApoE4-C6 cells. In conclusion, the increased melatonin level in ApoE4-C6 cells results from up-regulation of NAT expression, a key enzyme for melatonin synthesis, and down-regulation of MAOA and MAOB expression, the metabolic enzyme for its precursor serotonin.

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Section: Discussionsupporting

confidence: 52%

Apolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells

Liu¹,

Meng²,

Wang

et al. 2012

Journal of Pineal Research

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“…Other mechanisms, in addition to the one of the higher progesterone levels observed in our study, could be suggested. The presence of the ApoE4 allele was related to a later age at menopause and a longer reproductive lifespan in Chinese women [67]. Having the ApoE4 Table 2.…”

Section: Discussionmentioning

confidence: 97%

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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“…The APOE ε4 allele can also have an additive effect on LOAD-associated brain glucose hypometabolism (Ossenkoppele et al, 2013;Reiman et al, 2005), as this allele contributes to glucose hypometabolism even in the absence of neurodegeneration and cognitive decline (Knopman et al, 2014;Sundermann et al, 2018). As the ε4 allele is associated with delayed menopause (Meng et al, 2012), it perhaps lengthens the perimenopausal transition and worsens glucose hypometabolism. A proposed mechanism underlying ε4-associated hypometabolism is the inhibition of the PPAR-γ/PGC-1α (PPARGC1A) pathway (Box 1), which supports neuronal function by promoting mitochondrial energy production (Wu et al, 2018).…”

Section: Apoe ε4mentioning

confidence: 99%

Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders

Gamache

Yun

Chiba‐Falek

2020

Disease Models &Amp; Mechanisms

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The importance of apolipoprotein E (APOE) in late-onset Alzheimer's disease (LOAD) has been firmly established, but the mechanisms through which it exerts its pathogenic effects remain elusive. In addition, the sex-dependent effects of APOE on LOAD risk and endophenotypes have yet to be explained. In this Review, we revisit the different aspects of APOE involvement in neurodegeneration and neurological diseases, with particular attention to sex differences in the contribution of APOE to LOAD susceptibility. We discuss the role of APOE in a broader range of age-related neurodegenerative diseases, and summarize the biological factors linking APOE to sex hormones, drawing on supportive findings from rodent models to identify major mechanistic themes underlying the exacerbation of LOAD-associated neurodegeneration and pathology in the female brain. Additionally, we list sex-by-genotype interactions identified across neurodegenerative diseases, proposing APOE variants as a shared etiology for sex differences in the manifestation of these diseases. Finally, we present recent advancements in ‘omics’ technologies, which provide a new platform for more in-depth investigations of how dysregulation of this gene affects the development and progression of neurodegenerative diseases. Collectively, the evidence summarized in this Review highlights the interplay between APOE and sex as a key factor in the etiology of LOAD and other age-related neurodegenerative diseases. We emphasize the importance of careful examination of sex as a contributing factor in studying the underpinning genetics of neurodegenerative diseases in general, but particularly for LOAD.

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ApoE genotypes are associated with age at natural menopause in Chinese females

Cited by 15 publications

References 46 publications

Apolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells

Apolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells

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

Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders

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