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Archives of Gynecology and Obstetrics

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01.09.2015 | General Gynecology

Identification of biological processes and genes for gestational diabetes mellitus

verfasst von: Yile Su, Yuanzhen Zhang

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 3/2015

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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.

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 61:3167–3171PubMedCentralPubMedCrossRef

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 352:2477–2486CrossRef

Landon MB, Spong CY, Thom E et al (2009) A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 361:1339–1348PubMedCentralPubMedCrossRef

Kühl C (1991) 2 Aetiology of gestational diabetes. Baillieres Clin Obstet Gynaecol 5:279–292PubMedCrossRef

Radaelli T, Varastehpour A, Catalano P, Hauguel-De Mouzon S (2003) Gestational diabetes induces placental genes for chronic stress and inflammatory pathways. Diabetes 52:2951–2958PubMedCrossRef

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 10:185–197PubMedCrossRef

Chen X, Scholl TO (2005) Oxidative stress: changes in pregnancy and with gestational diabetes mellitus. Curr Diabetes Rep 5:282–288CrossRef

Miehle K, Stepan H, Fasshauer M (2012) Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia. Clin Endocrinol (Oxf) 76:2–11CrossRef

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 84:1695–1699PubMed

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 50:972–979PubMedCrossRef

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 355:180–187PubMedCentralPubMedCrossRef

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 99:151–157PubMedCrossRef

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:P3PubMedCrossRef

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–D815PubMedCentralPubMedCrossRef

15.

Kohl M, Wiese S, Warscheid B (2011) Cytoscape: software for visualization and analysis of biological networks. Methods Mol Biol 696:291–303PubMedCrossRef

16.

Bader GD, Hogue CW (2003) An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics 4:2PubMedCentralPubMedCrossRef

17.

Maere S, Heymans K, Kuiper M (2005) BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 21:3448–3449PubMedCrossRef

18.

Butte NF (2000) Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr 71:1256s–1261sPubMed

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 143:930–940CrossRef

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 34:245–253PubMedCrossRef

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)

22.

Reidy SP, Weber J-M (2000) Leptin: an essential regulator of lipid metabolism. Comp Biochem Physiol A Mol Integr Physiol 125:285–298PubMedCrossRef

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 28:34–38PubMedCrossRef

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):448–459PubMedCentralPubMedCrossRef

25.

Yakar S, Liu J-L, Fernandez AM et al (2001) Liver-specific igf-1 gene deletion leads to muscle insulin insensitivity. Diabetes 50:1110–1118PubMedCrossRef

26.

Kahl CR, Means AR (2003) Regulation of cell cycle progression by calcium/calmodulin-dependent pathways. Endocr Rev 24:719–736PubMedCrossRef

27.

Wagner EF, Eferl R (2005) Fos/AP-1 proteins in bone and the immune system. Immunol Rev 208:126–140PubMedCrossRef

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 401:73–76PubMedCrossRef

29.

Fantuzzi G, Faggioni R (2000) Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol 68:437–446PubMed

30.

Levite M, Cahalon L, Hershkoviz R, Steinman L, Lider O (1998) Neuropeptides, via specific receptors, regulate T cell adhesion to fibronectin. J Immunol 160:993–1000PubMed

Titel: Identification of biological processes and genes for gestational diabetes mellitus
verfasst von: Yile Su
Yuanzhen Zhang
Publikationsdatum: 01.09.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Archives of Gynecology and Obstetrics / Ausgabe 3/2015
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-015-3649-6

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Springer Medizin

Identification of biological processes and genes for gestational diabetes mellitus

Abstract