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

Clinical Epigenetics
M OuniP Bougnères

Abstract

Even if genetics play an important role, individual variation in stature remains unexplained at the molecular level. Indeed, genome-wide association study (GWAS) have revealed hundreds of variants that contribute to the variability of height but could explain only a limited part of it, and no single variant accounts for more than 0.3% of height variance. At the interface of genetics and environment, epigenetics contributes to phenotypic diversity. Quantifying the impact of epigenetic variation on quantitative traits, an emerging challenge in humans, has not been attempted for height. Since insulin-like growth factor 1 (IGF1) controls postnatal growth, we tested whether the CG methylation of the two promoters (P1 and P2) of the IGF1 gene is a potential epigenetic contributor to the individual variation in circulating IGF1 and stature in growing children. Child height was closely correlated with serum IGF1. The methylation of a cluster of six CGs located within the proximal part of the IGF1 P2 promoter showed a strong negative association with serum IGF1 and growth. The highest association was for CG-137 methylation, which contributed 13% to the variance of height and 10% to serum IGF1. CG methylation (studied in children undergo...Continue Reading

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Citations

Nov 19, 2015·European Journal of Endocrinology·Jan M WitSarina G Kant
Jul 29, 2015·Clinical Endocrinology·Meriem OuniPierre Bougnères
Oct 12, 2017·Journal of Developmental Origins of Health and Disease·D Montoya-WilliamsC J Mulligan
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Feb 24, 2017·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Susan JungRegina Trollmann
Sep 22, 2017·Diseases·Bodo C Melnik, Gerd Schmitz
May 2, 2018·Clinical Epigenetics·Catherine Le StunffPierre Bougnères
Jul 18, 2020·Clinical Epigenetics·Masato KantakeToshiaki Shimizu
May 17, 2021·Frontiers in Neuroendocrinology·Phoebe D EdwardsMelissa M Holmes
Dec 10, 2017·Best Practice & Research. Clinical Endocrinology & Metabolism·Bodo C Melnik, Gerd Schmitz

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Methods Mentioned

BETA
transfection
PCR
biopsies
transfections

Software Mentioned

PyroQ CpG

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