title: Alteration in Expression and Methylation of IGF2/H19 in Placenta and Umbilical Cord Blood Are Associated with Macrosomia Exposed to Intrauterine Hyperglycemia.
abstract: OBJECTIVE
  Macrosomia is one of the most common complications in gestational diabetes mellitus. Insulin-like growth factor 2 and H19 are two of the imprinted candidate genes that are involved in fetal growth and development. Change in methylation at differentially methylated region of the insulin-like growth factor 2 and H19 has been proved to be an early event related to the programming of metabolic profile, including macrosomia and small for gestational age in offspring. Here we hypothesize that alteration in methylation at differentially methylated region of the insulin-like growth factor 2 and H19 is associated with macrosomia induced by intrauterine hyperglycemia.
  
  
  RESULTS
  The expression of insulin-like growth factor 2 is significant higher in gestational diabetes mellitus group (GDM group) compared to normal glucose tolerance group (NGT group) both in umbilical cord blood and placenta, while the expression of H19 is significant lower in GDM group in umbilical cord blood. The expression of insulin-like growth factor 2 is significant higher in normal glucose tolerance with macrosomia group (NGT-M) compared to normal glucose tolerance with normal birthweight group (NGT-NBW group) both in placenta and umbilical cord blood. A model with interaction term of gene expression of IGF2 and H19 found that IGF2 and the joint action of IGF2 and H19 in placenta showed significantly relationship with GDM/NGT and GDM-NBW/NGT-NBW. A borderline significant association was seen among IGF2 and H19 in cord blood and GDM-M/NGT-M. The methylation level at different CpG sites of insulin-like growth factor 2 and H19 in umbilical cord blood was also significantly different among groups. Based on the multivariable linear regression analysis, the methylation of the insulin-like growth factor 2 / H19 is closely related to birth weight and intrauterine hyperglycemia.
  
  
  CONCLUSIONS
  We confirmed the existence of alteration in DNA methylation in umbilical cord blood exposed to intrauterine hyperglycemia and reported a functional role in regulating gene associated with insulin-like growth factor 2/H19. Both of these might be the underlying pathogenesis of macrosomia. We also provided the evidence of strong associations between methylation of insulin-like growth factor 2/H19 and macrosomia induced by intrauterine hyperglycemia.
authors: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
authors: Rina
authors: R
authors: Su
authors: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
authors: Chen
authors: C
authors: Wang
authors: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
authors: Hui
authors: H
authors: Feng
authors: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
authors: Li
authors: L
authors: Lin
authors: Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Florida, United States of America.
authors: Xinyue
authors: X
authors: Liu
authors: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
authors: Yumei
authors: Y
authors: Wei
authors: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
authors: Huixia
authors: H
authors: Yang
mesh_terms: D000328:Adult; D019175:DNA Methylation; D016640:Diabetes, Gestational / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005320:Fetal Macrosomia / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism* / Q000473:pathology; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis*; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D062085:RNA, Long Noncoding / Q000096:biosynthesis*; D014470:Umbilical Cord / Q000378:metabolism* / Q000473:pathology
chemical_list: C094335:H19 long non-coding RNA; C035170:IGF2 protein, human; D062085:RNA, Long Noncoding; D007335:Insulin-Like Growth Factor II