title: Increased methylation at differentially methylated region of GNAS in infants born to gestational diabetes.
abstract: BACKGROUND
  Offspring of pregnancy complicated with gestational diabetes (GDM) are at high risk for metabolic diseases. The mechanisms behind the association of intrauterine exposure to GDM and high risk of health problems in later life remain largely unknown. The aim of this study was to clarify the alteration in methylation levels at differentially methylated regions (DMRs) of GNAS and IGF2 in fetuses of GDM women and to explore the possible mechanisms linking maternal GDM with high risk of metabolic diseases in later life of GDM offspring.
  
  
  METHODS
  Lymphocytes were isolated from umbilical cord blood of infants born to 87 women with GDM and 81 women with normal pregnancy. Genomic DNA was extracted and DNA methylation levels of GNAS and IGF2 DMRs were determined by Massarray quantitative methylation analysis.
  
  
  RESULTS
  The methylation levels were detected in 7 CpG sites of GNAS DMRs and 6 sites of IGF2 DMRs. Methylation levels were significantly higher at sites 4, 5 and 7 of GNAS DMR in GDM compared to normal pregnancy (P = 0.007, 0.008 and 0.008, respectively). The methylation level at site 4 of GNAS was significantly correlated with the presence of GDM (P = 0.003), the methylation levels at site 5 and 7 were significantly correlated with the presence of GDM (P = 0.002 for both) and gestational age (P = 0.027 for both). There was no significant difference in any sites of IGF2 DMR (P > 0.05 for all).
  
  
  CONCLUSIONS
  We concluded maternal GDM-induced hypermethylation at GNAS DMR and this condition may be among the mechanisms associating maternal GDM with increased risk of metabolic diseases in later life of offspring.
authors.affiliation: Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, 310006, Zhejiang Province, China. chendq@zju.edu.cn.
authors.forename: Danqing
authors.initials: D
authors.lastname: Chen
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. az1758@gmail.com.
authors.forename: Aiping
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Shaoxing Women and Children's Hospital, Shaoxing, China. fangming0005@sina.com.
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.affiliation: Huzhou Maternity and Child Care Hospital, Huzhou, China. fr@hzfby.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Fang
authors.affiliation: Jiaxing Maternity and Child Care Hospital, Jiaxing, China. jiangliqin@medmail.com.cn.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Ge
authors.affiliation: Ningbo Women and Children's Hospital, Ningbo, China. jiangyuan-b05@163.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China. mingyi-hong@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, 310006, Zhejiang Province, China. han363654325@163.com.
authors.forename: Cong
authors.initials: C
authors.lastname: Han
authors.affiliation: Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, 310006, Zhejiang Province, China. 188677077@163.com.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Ye
authors.affiliation: Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, 310006, Zhejiang Province, China. hhf@zju.edu.cn.|Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, China. hhf@zju.edu.cn.
authors.forename: Hefeng
authors.initials: H
authors.lastname: Huang
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China. superliuyun@gmail.com.|Department of Biochemistry and Molecular Biology, Key Laboratory of Molecular Medicine, The Ministry of Education, Fudan University Shanghai Medical College, 303 Mingdao Building, 138 Yixueyuan Road, Shanghai, 200032, PR China. superliuyun@gmail.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, 310006, Zhejiang Province, China. mydong.cn@hotmail.com.|Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, China. mydong.cn@hotmail.com.|Key Laboratory of Women's Reproductive Health of Zhejiang Province, Hangzhou, China. mydong.cn@hotmail.com.
authors.forename: Minyue
authors.initials: M
authors.lastname: Dong
mesh_terms: D000328:Adult; D002864:Chromogranins; D018899:CpG Islands; D019175:DNA Methylation; D016640:Diabetes, Gestational / Q000175:diagnosis*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008661:Metabolism, Inborn Errors / Q000209:etiology*; D011247:Pregnancy
chemical_list: D002864:Chromogranins; C035170:IGF2 protein, human; D007335:Insulin-Like Growth Factor II; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs