6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      IGF1 gene is epigenetically activated in preterm infants with intrauterine growth restriction

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          IGF1 is a key molecule in the regulation of growth and metabolism. Low IGF1 secretion is known to cause growth restriction in childhood, as well as deregulated lipid metabolism, cardiovascular disease, and diabetes in adulthood. The IGF1 gene P2 promoter is highly methylated, resulting in low secretion of IGF1 in small infants and children. However, it is unknown when this methylation occurs. The aim of study was to clarify the point when this epigenetic program occurs during intrauterine development.

          We analyzed 56 preterm infants born before 32 weeks of gestation, including 19 intrauterine growth restriction (IUGR) infants whose birth weights were lower than − 2SD calculated by the Japanese datasets. We extracted genomic DNA from whole blood at birth; methylation of the six CpG sites in the IGF1 P2 promoter was analyzed by the bisulfite amplicon method using the MiSeq platform.

          Results

          In contrast to term infants and children, the methylation of all six CpG sites positively correlated with body weight and body length at birth. IGF1 P2 promoter methylation levels were significantly reduced in all six CpG sites in infants with IUGR.

          Conclusions

          These findings indicated that the IGF1 gene is epigenetically activated before 32 weeks of gestation in infants with IUGR and that the activated gene may become suppressed after this time point. This study may provide new insights to prevent the onset of adult diseases and to aid in nutritional management for preterm birth infants in neonatal intensive care units.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: not found
          • Article: not found

          Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene.

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth.

            Insulin-like growth factor I (IGF-I) is necessary for normal development of retinal blood vessels in mice and humans. Because retinopathy of prematurity (ROP) is initiated by abnormal postnatal retinal development, we hypothesized that prolonged low IGF-I in premature infants might be a risk factor for ROP. We conducted a prospective, longitudinal study measuring serum IGF-I concentrations weekly in 84 premature infants from birth (postmenstrual ages: 24-32 weeks) until discharge from the hospital. Infants were evaluated for ROP and other morbidity of prematurity: bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC). Low serum IGF-I values correlated with later development of ROP. The mean IGF-I +/- SEM level during postmenstrual ages 30-33 weeks was lowest with severe ROP (25 +/- 2.41 micro g/L), 29 +/- 1.76 micro g/L with moderate ROP, and 33 +/- 1.72 micro g/L with no ROP. The duration of low IGF-I also correlated strongly with the severity of ROP. The interval from birth until serum IGF-I levels reached >33 micro g/L was 23 +/- 2.6 days for no ROP, 44 +/- 4.8 days for moderate ROP, and 52 +/- 7.5 days for severe ROP. Each adjusted stepwise increase of 5 micro g/L in mean IGF-I during postmenstrual ages 30 to 33 weeks decreased the risk of proliferative ROP by 45%. Other complications (NEC, BPD, IVH) were correlated with ROP and with low IGF-I levels. The relative risk for any morbidity (ROP, BPD, IVH, or NEC) was increased 2.2-fold (95% confidence interval: 1.41-3.43) if IGF-I was
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Epigenetic inheritance and the missing heritability

              Genome-wide association studies of complex physiological traits and diseases consistently found that associated genetic factors, such as allelic polymorphisms or DNA mutations, only explained a minority of the expected heritable fraction. This discrepancy is known as “missing heritability”, and its underlying factors and molecular mechanisms are not established. Epigenetic programs may account for a significant fraction of the “missing heritability.” Epigenetic modifications, such as DNA methylation and chromatin assembly states, reflect the high plasticity of the genome and contribute to stably alter gene expression without modifying genomic DNA sequences. Consistent components of complex traits, such as those linked to human stature/height, fertility, and food metabolism or to hereditary defects, have been shown to respond to environmental or nutritional condition and to be epigenetically inherited. The knowledge acquired from epigenetic genome reprogramming during development, stem cell differentiation/de-differentiation, and model organisms is today shedding light on the mechanisms of (a) mitotic inheritance of epigenetic traits from cell to cell, (b) meiotic epigenetic inheritance from generation to generation, and (c) true transgenerational inheritance. Such mechanisms have been shown to include incomplete erasure of DNA methylation, parental effects, transmission of distinct RNA types (mRNA, non-coding RNA, miRNA, siRNA, piRNA), and persistence of subsets of histone marks.
                Bookmark

                Author and article information

                Contributors
                kantake@juntendo.ac.jp
                nikeda@juntendo.ac.jp
                h-nakaoka@po.kyoundo.jp
                nookawa@juntendo.ac.jp
                t-tanaka@juntendo.ac.jp
                026272gg@gmail.com
                hshoji@juntendo.ac.jp
                tshimizu@juntendo.ac.jp
                Journal
                Clin Epigenetics
                Clin Epigenetics
                Clinical Epigenetics
                BioMed Central (London )
                1868-7075
                1868-7083
                16 July 2020
                16 July 2020
                2020
                : 12
                : 108
                Affiliations
                [1 ]GRID grid.482667.9, Neonatal Medical Center, , Juntendo University Shizuoka Hospital, ; 1192 Nagaoka, Izunokuni, Shizuoka 410-2295 Japan
                [2 ]GRID grid.288127.6, ISNI 0000 0004 0466 9350, Human Genetics Laboratory, Department of Genomics and Evolutionary Biology, , National Institute of Genetics, ; 1111 Yata, Mishima, Shizuoka 411-8540 Japan
                [3 ]GRID grid.419521.a, ISNI 0000 0004 1763 8692, Department of Cancer Genome Research, Sasaki Institute, , Sasaki Foundation, ; 2-2 Kandasurugadai, Chiyoda-ku, Tokyo, 101-0062 Japan
                [4 ]GRID grid.482667.9, Perinatal Medical Center, , Juntendo University Shizuoka Hospital, ; 1192 Nagaoka, Izunokuni, Shizuoka 410-2295 Japan
                [5 ]GRID grid.258269.2, ISNI 0000 0004 1762 2738, Department of Pediatrics and Adolescent Medicine, , Juntendo University, ; 3-1-3 Hongo, Bunkyo-ku, Tokyo, 113-8431 Japan
                Author information
                http://orcid.org/0000-0002-9392-3562
                Article
                901
                10.1186/s13148-020-00901-w
                7364555
                32678007
                a8368879-38a0-4d0f-bca7-ea6a6bbf0f9b
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 23 April 2020
                : 8 July 2020
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Genetics
                igf1,p2 promoter,methylation,epigenetics,intrauterine growth restriction,iugr,preterm,newborn infant
                Genetics
                igf1, p2 promoter, methylation, epigenetics, intrauterine growth restriction, iugr, preterm, newborn infant

                Comments

                Comment on this article