The role of genetic factors in age at natural menopause

Bruin, Jan Peter de; Bovenhuis, H.; Noord, P.A.H. van; Pearson, P. L.; Arendonk, J.A.M. van; Velde, Egbert R. te; Kuurman, W.W.; Dorland, M.

doi:10.1093/humrep/16.9.2014

Cited by 266 publications

(137 citation statements)

References 16 publications

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“…Twin study has suggested that more than 60% of the AANM variation could be explained by the genetic factors [14][15][16]. However, very few genes have been reported to affect AANM [17][18][19][20].…”

Section: Discussionmentioning

confidence: 99%

“…Family study showed that the menopausal ages of daughters were significantly correlated with mothers' [13]. Heritability estimates of AANM ranged from 0.63 to 0.87, suggesting a strong genetic control [14][15][16]. To date, the exact genes involved remain unknown, though some candidate genes underlying AANM have been proposed, such as ESR1 (estrogen receptor alpha), CYP1B1 (cytochrome P450, family 1, subfamily B, poly-peptide 1), Factor V Leiden, and FMR1 (fragile X mental retardation 1) [17][18][19][20].…”

Section: Introductionmentioning

confidence: 98%

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HDC gene polymorphisms are associated with age at natural menopause in Caucasian women

Zhang

Xiong

Wang

et al. 2006

Biochemical and Biophysical Research Communications

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Histidine decarboxylase gene (HDC) encodes histidine decarboxylase which is the crucial enzyme for the biosynthesis of histidine. Studies have shown that histamine is likely to be involved in the regulation of reproduction system. To find the possible correlation between HDC gene and AANM (age at natural menopause), we selected 265 postmenopausal women from 131 nuclear families and performed a transmission disequilibrium test. Significant within-family associations with AANM for SNP rs854163 and SNP rs854158 of HDC gene were observed (P values = 0.0018 and 0.0197, respectively). After 1000 permutations, SNP rs854163 still remained significant within-family association with AANM. Consistently, we also detected a significant within-family association between haplotype block 2 (defined by SNP rs854163 and rs860526) and AANM in the haplotype analyses (P value = 0.0397). Our results suggest that the HDC gene polymorphisms are significantly associated with AANM in Caucasian women. KeywordsHDC; Association; Age at natural menopause; SNP Menopause status is one important anthropological variable influencing the overall health of women, especially those in advanced ages. Abnormal low age at natural menopause (AANM) correlates with female infertility due to ovarian aging [1]. Early menopause was also reported to be associated with the increased risks of fracture [2,3], coronary heart disease [4,5], and disorders of the central nervous system [6,7]. In addition, the Caucasian women with menopause ages of about 40-44 years have 4% higher risk of mortality than those with menopause ages of about 50-54 years [8].There is a wide variation in AANM, varying between 40 and 60 years. Extensive studies have been conducted to search for the predictors of AANM. Some lifestyle factors were reported to be associated with AANM, such as obesity, smoking, alcohol consumption, and breastfeeding [9][10][11]. However, these lifestyle factors just accounted for a small part of the large variation in AANM [12]. Additionally, genetic factors were found to play an important role in the variation of AANM. Family study showed that the menopausal ages of daughters were significantly correlated with mothers' [13]. Heritability estimates of AANM ranged from 0.63 to 0.87, suggesting a strong genetic control [14][15][16]. To date, the exact genes involved remain unknown, though some candidate genes underlying AANM have been proposed, such as ESR1 (estrogen receptor alpha), CYP1B1 (cytochrome P450, family 1, subfamily B, poly-peptide 1), Factor V Leiden, and FMR1 (fragile X mental retardation 1) [17][18][19][20].Histidine decarboxylase (HDC) gene encodes histidine decarboxylase, which is the crucial enzyme for synthesis of histamine in human body. As an important bioactive substance, histamine is crucial to various physiological activities [21]. It has been found that histamine directly stimulated the secretion of GnRH (gonadotropin-releasing hormone), which is the key molecule in the regulation of gonadal hormone release [22]. Furthermore, st...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

HDC gene polymorphisms are associated with age at natural menopause in Caucasian women

Zhang

Xiong

Wang

et al. 2006

Biochemical and Biophysical Research Communications

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“…We identified sister-and twin-pairs, of which both siblings participated in DOM, using probabilistic matching [17]. All data used for matching had been collected at the time of recruitment in DOM.…”

Section: Subjectsmentioning

confidence: 99%

Heritable Aspects of Dysplastic Breast Glandular Tissue (DY)

Haars

Noord

Gils

et al. 2004

Breast Cancer Res Treat

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SummaryBreast parenchymal patterns, as visible on mammograms, are determined by the relative amount of radiodense, glandular dysplastic tissue (DY). High percentages of DY are related to higher breast cancer risk. Previous studies reported heritable influences on DY of 32-67%, depending on the family relationship that was studied.We assessed heritability in 466 sister-, 25 dizygotic twin-and 26 monozygotic twin-pairs participating in a population-based breast cancer screening program; the DOM project (Diagnostic Investigation Mamma Carcinoma).The heritability was estimated for non-twin sisters, dizygotic and monozygotic twins seperately by computing correlations between siblings from the dichotomous DY-score (high risk versus low risk). This was done using methods based on the number of shared genes per sibtype.Heritability estimates were 38, 34 and 88% for sisters, dizygotic twins and monozygotic twins respectively. Heritability estimates from models that combine monozygotic twins with dizygotic twins or sisters indicated that dominant gene effects, genetic interactions or gene-environment effects could be involved. Parity appeared to have an effect on the heritabile influence with estimates ranging from 90% in sisters that were both nulliparous, to 2% in sisterpairs discordant for nulliparity. These result indicate a substantial genetic influence on DY, but with a possible modifying ability of other factors, such as parity.

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“…In guppies, for example, the presence of predators results in a delay in the decline in reproductive potential compared with females in populations where predators are absent (Reznick et al, 2006). In humans, phenotypic variation in age at natural menopause also appears to be affected by factors such as smoking and diet (Nagata et al, 2000;Gold et al, 2001;de Bruin et al, 2001;Kok et al, 2005). The variation underlying rates of fertility loss are not only environmental.…”

Section: Introductionmentioning

confidence: 99%

“…The variation underlying rates of fertility loss are not only environmental. The age of onset of natural menopause in humans can be predicted by family history, with heritability estimates ranging from 0.30 to 0.85 (Kirk et al, 2001;de Bruin et al, 2001;Kok et al, 2005;Pettay et al, 2005;Broekmans et al, 2007). Linkage analysis of age at natural menopause has identified two significant quantitative trait loci influencing age at menopause (van Asselt et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Quantitative genetic variation in the control of ovarian apoptosis under different environments

et al. 2009

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Fertility loss in otherwise healthy individuals can be an evolutionary conundrum. Most studies on the evolution of postreproductive lifespan focus on the fitness effects of survival past the age of last reproduction. A complementary approach, which has been largely neglected, is to develop an understanding of the nature of variation in the mechanism underlying loss of fertility, ovarian apoptosis. Variation in the genetics underlying the regulation of ovarian apoptosis could hold the key to understanding the evolution of midlife fertility loss. We estimated quantitative genetic variation in the regulation of ovarian apoptosis in females of the cockroach Nauphoeta cinerea, an insect with reproductive cycles. We have earlier shown that delaying reproduction incites loss of fertility. Here, we forced females to delay reproduction under conditions of excess or limited food and examined apoptosis under both conditions. We found substantial additive genetic variation in levels of apoptosis when females experienced a limited period of starvation during sexual maturation but not when females had unlimited access to food. Hence, selection could act on the regulation of ovarian apoptosis to change the rate of fertility loss with age at least under some environmental circumstances. Our results suggest that an understanding of how loss of fertility evolves requires an understanding of the interaction between genes involved in the regulation of apoptosis and environmental factors such as diet.

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The role of genetic factors in age at natural menopause

Abstract: According to our findings, a woman with a family history of early menopause risks early menopause and consequently early reproductive failure herself.

Cited by 266 publications

References 16 publications

HDC gene polymorphisms are associated with age at natural menopause in Caucasian women

HDC gene polymorphisms are associated with age at natural menopause in Caucasian women

Heritable Aspects of Dysplastic Breast Glandular Tissue (DY)

Quantitative genetic variation in the control of ovarian apoptosis under different environments

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