IJCRR - 7(8), April, 2015
Pages: 23-27
FUNCTIONAL ANNOTATION OF PROTOCADHERIN BETA GENES HYPERMETHYLATION AND THEIR SIGNIFICANCE IN NEONATAL SEPSIS
Author: Benet Bosco Dhas D., Hiasindh Ashmi A., Vishnu Bhat B., Subhash Chandra Parija
Category: Healthcare
[Download PDF]
Abstract:
Background: Apart from genetic factors, epigenetic mechanisms like DNA methylation are now being established for their association with human diseases. Despite advance in medical research, sepsis still remains the major cause of neonatal mortality. In this study, the role of DNA methylation in neonatal sepsis was studied in an epigenome wide scale and the candidate genes were functionally annotated.
Methods: The methylation status was analyzed in babies with and without sepsis in epigenome wide scale using Illumina Infinium Human Methylation 450K methylation microarray. The microarray data was functionally annotated and interpreted for their
biological significance using the bioinformatics softwares and databases like DAVID v6.7, GeneMania, KEGG, etc.
Results: Functional annotation of methylation microarray data revealed that the protocadherin beta group of genes was hypermethylated in babies with neonatal sepsis. Protocadherin beta genes was found to be associated with calcium dependent cell to cell adhesion which is important in signaling pathways like leukocyte migration during sepsis.
Conclusion: DNA methylation might play critical roles in neonatal sepsis which was obvious from differential methylation of candidate genes like protocadherins, modifying the associated biological pathways.
Keywords: EWAS, CpG methylation, Neonatal sepsis, Protocadherins, Leukocyte adhesion molecules
Citation:
Benet Bosco Dhas D., Hiasindh Ashmi A., Vishnu Bhat B., Subhash Chandra Parija. FUNCTIONAL ANNOTATION OF PROTOCADHERIN BETA GENES HYPERMETHYLATION AND THEIR SIGNIFICANCE IN NEONATAL SEPSIS International Journal of Current Research and Review. 7(8), April, 23-27
References:
1. BB Dhas, Ashmi AH, Bhat BV, Kalaivani S, Parija SC. Comparison of genomic DNA methylation pattern among septic and non-septic newborns - an Epigenome wide association study. Genomics Data 2015;3:36–40.
2. Maekita T, Nakazawa K, Mihara M, Nakajima T, Yanaoka K, Iguchi M, et al.. High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res 2006; 12: 989–995.
3. Chan AO, Lam SK, Wong BC, Wong WM, Yuen MF, Yeung YH, et al. Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer. Gut 2003; 52: 502–506.
4. Yao Y, Tao H, Park DI, Sepulveda JL, Sepulveda AR. Demonstration and characterization of mutations induced by Helicobacter pylori organisms in gastric epithelial cells. Helicobacter 2006; 11: 272–286.
5. Yan J, Zhang M, Zhang J, Chen X, Zhang X. Helicobacter pylori infection promotes methylation of
6. Takahashi K, Sugi Y, Nakano K, Tsuda M, Kurihara K, Hosono A, et al. Epigenetic control of the host gene by commensal bacteria in large intestinal epithelial cells. J Biol Chem 2011; 286: 35755–35762.
7. Jelinek J, Li J, Mnjoyan Z, Issa JP, Prchal JT, AfsharKharghan V. Epigenetic control of PRV-1 expression on neutrophils. Exp Hematol 2007;35:1677–83.
8. El Gazzar M, Yoza BK, Chen X, Hu J, Hawkins GA, McCall CE. G9a and HP1 couple histone and DNA methylation to TNFalpha transcription silencing during endotoxin tolerance. J Biol Chem 2008;283:32198–208.
9. Bierne H, Hamon M, Cossart P. Epigenetics and bacterial infections. Cold Spring Harb Perspect Med 2012;2:1–24.
10. Halbleib JM, Nelson WJ. Cadherins in development: cell adhesion, sorting, and tissue morphogenesis. Genes Dev 2006;20:3199–214.
11. Ying J, Gao Z, Li H, Srivastava G, Murray PG, Goh HK, et al. Frequent epigenetic silencing of protocadherin 10 by methylation in multiple haematologic malignancies. Br J Haematol 2007;136:829–32.
12. Zarbock A, Ley K. Neutrophil adhesion and activation under flow. Microcirculation 2009;16:31–42.
13. Liu L, Kubes P. Molecular mechanisms of leukocyte recruitment: organ-specific mechanisms of action. Thromb Haemost 2003;89:213–20.
14. Mühl D, Woth G, Drenkovics L, Varga A, Ghosh S, Csontos C, et al. Comparison of oxidative stress and leukocyte activation in patients with severe sepsis and burn injury. Indian J Med Res 2011;134:69–78.
15. Benjamim CF, Silva JS, Fortes ZB, Oliveira MA, Ferreira SH, Cunha FQ. Inhibition of leukocyte rolling by nitric oxide during sepsis leads to reduced migration of active microbicidal neutrophils. Infect Immun 2002;70(7):3602–10.
16. Bierhaus A, Schiekofer S, Schwaninger M, Andrassy M, Humpert PM, Chen J, et al. Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB. Diabetes 2001;50:2792–808.
17. Yu G, Tseng GC, Yu YP, Gavel T, Nelson J, Wells A, et al. CSR1 suppresses tumor growth and metastasis of prostate cancer. Am J Pathol 2006;168:597–607.
|