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Archives of Gynecology and Obstetrics

, Volume 292, Issue 3, pp 635–640 | Cite as

Identification of biological processes and genes for gestational diabetes mellitus

  • Yile Su
  • Yuanzhen ZhangEmail author
General Gynecology

Abstract

Aim

Gestational diabetes mellitus (GDM) is one of the most usual complications of pregnancy, while the correlations between genes and their known biological processes need to be further elucidated.

Methods

In the current study, microarray data GSE2956 containing a list of 435 significantly modified genes (differentially expressed genes, DEGs) were used. Genes that correspond to official gene symbols were chosen and were functional annotated for Gene Ontology (GO) and pathway analyses (p ≤ 0.05). Then, the protein–protein interaction (PPI) network and the sub network were constructed and analyzed (combined score ≥0.4).

Results

A total of 405 DEGs including 239 up-regulated and 166 down-regulated genes were screened, and they were found mainly related to adhesion and motion, stimulus–response, and wound healing, etc. Besides, a PPI network containing 217 nodes and 644 lines was obtained. Hub genes including fibronectin 1 (FN1) and insulin-like growth factor 1 (IGF1) were down-regulated, and leptin (LEP) and calmodulin 1 (CALM1) were up-regulated. Three modules in the PPI network were mined and similar functional terms enriched by DEGs of these modules were obtained.

Conclusion

GO terms relevant to translation and metabolic process and their related genes CREB1, ribosomal proteins and LEP, still the inflammation-related proteins (e.g., IGF1 and CALM1) and cell adhesion-related protein FN1 may work together and be essential for GDM. This study provides insight into the cooperative interactions of metabolism and immune responses and the pathogenesis of GDM.

Keywords

Gestational diabetes mellitus Protein–protein interaction Differentially expressed genes Module Gene ontology 

Notes

Conflict of interest

All authors declare that they have no conflict of interests to state.

References

  1. 1.
    Ziegler A-G, Wallner M, Kaiser I et al (2012) Long-term protective effect of lactation on the development of type 2 diabetes in women with recent gestational diabetes mellitus. Diabetes 61:3167–3171PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Crowther C, Hiller J, Moss J, Mcphee A, Jeffries W, Robinson J for the Australian Carbohydrate Intolerance Study in pregnant women (ACHOIS) Trila Group (2005) Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 352:2477–2486CrossRefGoogle Scholar
  3. 3.
    Landon MB, Spong CY, Thom E et al (2009) A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 361:1339–1348PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Kühl C (1991) 2 Aetiology of gestational diabetes. Baillieres Clin Obstet Gynaecol 5:279–292PubMedCrossRefGoogle Scholar
  5. 5.
    Radaelli T, Varastehpour A, Catalano P, Hauguel-De Mouzon S (2003) Gestational diabetes induces placental genes for chronic stress and inflammatory pathways. Diabetes 52:2951–2958PubMedCrossRefGoogle Scholar
  6. 6.
    Palomer X, González-Clemente J, Blanco-Vaca F, Mauricio D (2008) Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes Metab 10:185–197PubMedCrossRefGoogle Scholar
  7. 7.
    Chen X, Scholl TO (2005) Oxidative stress: changes in pregnancy and with gestational diabetes mellitus. Curr Diabetes Rep 5:282–288CrossRefGoogle Scholar
  8. 8.
    Miehle K, Stepan H, Fasshauer M (2012) Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia. Clin Endocrinol (Oxf) 76:2–11CrossRefGoogle Scholar
  9. 9.
    Festa A, Krugluger W, Shnawa N, Hopmeier P, Haffner SM, Schernthaner G (1999) Trp64Arg Polymorphism of the β 3-Adrenergic Receptor Gene in Pregnancy: association with Mild Gestational Diabetes Mellitus. J Clin Endocr Metab 84:1695–1699PubMedGoogle Scholar
  10. 10.
    Shaat N, Lernmark Karlsson E, Ivarsson S, Parikh H, Berntorp K, Groop L (2007) A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus. Diabetologia 50:972–979PubMedCrossRefGoogle Scholar
  11. 11.
    Männik J, Vaas P, Rull K, Teesalu P, Laan M (2012) Differential placental expression profile of human growth hormone Chorionic Somatomammotropin genes in pregnancies with pre-eclampsia and gestational diabetes mellitus. Mol Cell Endocrinol 355:180–187PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Pappa KI, Gazouli M, Anastasiou E, Iliodromiti Z, Antsaklis A, Anagnou NP (2013) The major circadian pacemaker ARNT-like protein-1 (BMAL1) is associated with susceptibility to gestational diabetes mellitus. Diabetes Res Clin Pract 99:151–157PubMedCrossRefGoogle Scholar
  13. 13.
    Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4:P3PubMedCrossRefGoogle Scholar
  14. 14.
    Franceschini A, Szklarczyk D, Frankild S et al (2013) STRING v9.1: protein–protein interaction networks, with increased coverage and integration. Nucleic Acids Res 41:D808–D815PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Kohl M, Wiese S, Warscheid B (2011) Cytoscape: software for visualization and analysis of biological networks. Methods Mol Biol 696:291–303PubMedCrossRefGoogle Scholar
  16. 16.
    Bader GD, Hogue CW (2003) An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics 4:2PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Maere S, Heymans K, Kuiper M (2005) BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 21:3448–3449PubMedCrossRefGoogle Scholar
  18. 18.
    Butte NF (2000) Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr 71:1256s–1261sPubMedGoogle Scholar
  19. 19.
    Garcia Dos Santos E, Dieudonne MN, Pecquery R, Le Moal V, Giudicelli Y, Lacasa DL (2002) Rapid nongenomic E2 effects on p42/p44 MAPK, activator protein-1, and cAMP response element binding protein in rat white adipocytes. Endocrinology 143:930–940CrossRefGoogle Scholar
  20. 20.
    Gau D, Lemberger T, Von Gall C et al (2002) Phosphorylation of CREB Ser142 regulates light-induced phase shifts of the circadian clock. Neuron 34:245–253PubMedCrossRefGoogle Scholar
  21. 21.
    Enquobahrie DA, Williams MA, Qiu C, Meller M, Sorensen TK (2009) Global placental gene expression in gestational diabetes mellitus. Am J Obstet Gynecol 200:206. e201–e206 (e213)Google Scholar
  22. 22.
    Reidy SP, Weber J-M (2000) Leptin: an essential regulator of lipid metabolism. Comp Biochem Physiol A Mol Integr Physiol 125:285–298PubMedCrossRefGoogle Scholar
  23. 23.
    Di Benedetto A, Russo G, Corrado F et al (2005) Inflammatory markers in women with a recent history of gestational diabetes mellitus. J Endocrinol Invest 28:34–38PubMedCrossRefGoogle Scholar
  24. 24.
    Magee TR, Ross MG, Wedekind L, Desai M, Kjos S, Belkacemi L (2014) Gestational diabetes mellitus alters apoptotic and inflammatory gene expression of trophobasts from human term placenta. J Diabetes Complications 28(4):448–459PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Yakar S, Liu J-L, Fernandez AM et al (2001) Liver-specific igf-1 gene deletion leads to muscle insulin insensitivity. Diabetes 50:1110–1118PubMedCrossRefGoogle Scholar
  26. 26.
    Kahl CR, Means AR (2003) Regulation of cell cycle progression by calcium/calmodulin-dependent pathways. Endocr Rev 24:719–736PubMedCrossRefGoogle Scholar
  27. 27.
    Wagner EF, Eferl R (2005) Fos/AP-1 proteins in bone and the immune system. Immunol Rev 208:126–140PubMedCrossRefGoogle Scholar
  28. 28.
    Shimomura I, Hammer RE, Ikemoto S, Brown MS, Goldstein JL (1999) Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 401:73–76PubMedCrossRefGoogle Scholar
  29. 29.
    Fantuzzi G, Faggioni R (2000) Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol 68:437–446PubMedGoogle Scholar
  30. 30.
    Levite M, Cahalon L, Hershkoviz R, Steinman L, Lider O (1998) Neuropeptides, via specific receptors, regulate T cell adhesion to fibronectin. J Immunol 160:993–1000PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Obstetrics and gynecologyZhongnan Hospital of Wuhan UniversityWuhanChina

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