The IGF1 P2 promoter is an epigenetic QTL for circulating IGF1 and human growth

Ouni, Meriem; Güneş, Yasemin; Belot, Marie-Pierre; Castell, Anne-Laure; Fradin, Delphine; Bougnères, Pierre

doi:10.1186/s13148-015-0062-8

Cited by 42 publications

(55 citation statements)

References 80 publications

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“…Remember that miRNA-148a directly targets the pivotal genes regulating triglyceride synthesis ( FAS ), cholesterol homeostasis ( LDLR ), cholesterol efflux ( ABCA1 ), and β-oxidation ( CTPA1 ) [106]. miRNA-148a via targeting DNMT1 and subsequent promoter hypomethylation enhances adipogenic gene expression including insulin ( INS ), insulin-like growth factor-1 ( IGF1 ), caveolin-1 ( CAV1 ), leptin ( LEP ), PPAR-γ2 ( PPARG2 ), fatty acid-binding protein 4 ( FABP4 ), and lipoprotein lipase ( LPL ) [170,174,175,179,243]. Additionally, milk miRNA-148a-mediated FTO promoter demethylation may further enhance RNA transcription of the key adipogenic transcription factors RUNX1T1, PPARγ, CEBPα, and PGC1α via erasing m 6 A marks on their target mRNAs.…”

Section: Milk-mediated Epigenetic Signaling and Diseases Of Civilmentioning

confidence: 99%

Milk’s Role as an Epigenetic Regulator in Health and Disease

2017

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Abstract:It is the intention of this review to characterize milk's role as an epigenetic regulator in health and disease. Based on translational research, we identify milk as a major epigenetic modulator of gene expression of the milk recipient. Milk is presented as an epigenetic "doping system" of mammalian development. Milk exosome-derived micro-ribonucleic acids (miRNAs) that target DNA methyltransferases are implicated to play the key role in the upregulation of developmental genes such as FTO, INS, and IGF1. In contrast to miRNA-deficient infant formula, breastfeeding via physiological miRNA transfer provides the appropriate signals for adequate epigenetic programming of the newborn infant. Whereas breastfeeding is restricted to the lactation period, continued consumption of cow's milk results in persistent epigenetic upregulation of genes critically involved in the development of diseases of civilization such as diabesity, neurodegeneration, and cancer. We hypothesize that the same miRNAs that epigenetically increase lactation, upregulate gene expression of the milk recipient via milk-derived miRNAs. It is of critical concern that persistent consumption of pasteurized cow's milk contaminates the human food chain with bovine miRNAs, that are identical to their human analogs. Commercial interest to enhance dairy lactation performance may further increase the epigenetic miRNA burden for the milk consumer.

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Section: Milk-mediated Epigenetic Signaling and Diseases Of Civilmentioning

confidence: 99%

Milk’s Role as an Epigenetic Regulator in Health and Disease

2017

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“…For IGF1, methylation of one of its promoters was found to be an epigenetic quantitative trait locus that modulates the amount of circulating IGF1 and partly explains the variation in human stature (Ouni et al 2015). As regards IGFBP3, alterations of DNA methylation in the promoter have been associated with degree of expression and with survival rates from various cancer forms in humans (Perks and Holly 2015; Tomii et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Prenatal arsenic exposure is associated with increased plasma IGFBP3 concentrations in 9-year-old children partly via changes in DNA methylation

et al. 2018

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Exposure to inorganic arsenic (As), a carcinogen and epigenetic toxicant, has been associated with lower circulating levels of insulin-like growth factor 1 (IGF1) and impaired growth in children of pre-school age. The aim of this study was to assess the potential impact of exposure to As on IGF1 and insulin-like growth factor-binding protein 3 (IGFBP3) as well as DNA methylation changes in 9-year-old children. To this end, we studied 9-year-old children from a longitudinal mother–child cohort in rural Bangladesh (n = 551). Prenatal and concurrent exposure to As was assessed via concentrations in maternal urine at gestational week 8 and in child urine at 9 years, measured by HPLC-HG-ICPMS. Plasma IGF1 and IGFBP3 concentrations were quantified with immunoassays. DNA methylation was measured in blood mononuclear cells at 9 years in a sub-sample (n = 113) using the Infinium HumanMethylation450K BeadChip. In multivariable-adjusted linear regression models, prenatal As (natural log-transformed), but not children’s concurrent urinary As, was positively associated with IGFBP3 concentrations (β = 76, 95% CI 19, 133). As concentrations were not associated with IGF1. DNA methylation analysis revealed CpGs associated with both prenatal As and IGFBP3. Mediation analysis suggested that methylation of 12 CpG sites for all children was mediator of effect for the association between prenatal As and IGFBP3. We also found differentially methylated regions, generally hypermethylated, that were associated with both prenatal As and IGFBP3. In all, our study revealed that prenatal exposure to As was positively associated with IGFBP3 concentrations in children at 9 years, independent of IGF1, and this association may, at least in part, be epigenetically mediated.Electronic supplementary materialThe online version of this article (10.1007/s00204-018-2239-3) contains supplementary material, which is available to authorized users.

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“…Another example is the epigenetic control of several parts of the IGF1 signalling pathway. The IGF1 P2 promotor is an epigenetic quantitative trait locus (QTL), and methylation of a cluster of six CGs located within the proximal part of this promoter shows a strong negative association with serum IGF1 and growth (232). In children with ISS CG-137 methylation in this promoter contributed 30% to the variance of the IGF1 response to GH in an IGF1 generation test (233).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

Wit

Oostdijk

Losekoot

et al. 2016

European Journal of Endocrinology

154

132

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The fast technological development, particularly single nucleotide polymorphism array, array-comparative genomic hybridization, and whole exome sequencing, has led to the discovery of many novel genetic causes of growth failure. In this review we discuss a selection of these, according to a diagnostic classification centred on the epiphyseal growth plate. We successively discuss disorders in hormone signalling, paracrine factors, matrix molecules, intracellular pathways, and fundamental cellular processes, followed by chromosomal aberrations including copy number variants (CNVs) and imprinting disorders associated with short stature. Many novel causes of GH deficiency (GHD) as part of combined pituitary hormone deficiency have been uncovered. The most frequent genetic causes of isolated GHD are GH1 and GHRHR defects, but several novel causes have recently been found, such as GHSR, RNPC3, and IFT172 mutations. Besides well-defined causes of GH insensitivity (GHR, STAT5B, IGFALS, IGF1 defects), disorders of NFkB signalling, STAT3 and IGF2 have recently been discovered. Heterozygous IGF1R defects are a relatively frequent cause of prenatal and postnatal growth retardation. TRHA mutations cause a syndromic form of short stature with elevated T 3 /T 4 ratio. Disorders of signalling of various paracrine factors (FGFs, BMPs, WNTs, PTHrP/IHH, and CNP/NPR2) or genetic defects affecting cartilage extracellular matrix usually cause disproportionate short stature. Heterozygous NPR2 or SHOX defects may be found in w3% of short children, and also rasopathies (e.g., Noonan syndrome) can be found in children without clear syndromic appearance. Numerous other syndromes associated with short stature are caused by genetic defects in fundamental cellular processes, chromosomal abnormalities, CNVs, and imprinting disorders.

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The IGF1 P2 promoter is an epigenetic QTL for circulating IGF1 and human growth

Cited by 42 publications

References 80 publications

Milk’s Role as an Epigenetic Regulator in Health and Disease

Milk’s Role as an Epigenetic Regulator in Health and Disease

Prenatal arsenic exposure is associated with increased plasma IGFBP3 concentrations in 9-year-old children partly via changes in DNA methylation

MECHANISMS IN ENDOCRINOLOGY: Novel genetic causes of short stature

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