Next generation sequencing of circulating of miRNAs - Towards novel celiac disease biomarkers.

Tan, I.L. (2015) Next generation sequencing of circulating of miRNAs - Towards novel celiac disease biomarkers. thesis, Medicine.

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Abstract

Background Celiac disease (CeD) is an immune mediated gluten induced enteropathy. The disease affects approximately 1% of the Caucasian population and occurs in genetically susceptible individuals only. Diagnosis in early stages of CeD is challenging, due to the clinical heterogeneity of CeD. If CeD could be detected at an early stage, severe consequences of CeD, such as chronic diarrhoea and failure to thrive could be prevented by quick initiation of a gluten free diet (GFD). However, no early biomarkers for CeD previous to enteropathy development are known. In the search for predictive disease biomarkers, circulating microRNAs (miRNAs) would be excellent candidates. In contrast to messengerRNA, miRNA is very stable in blood probably due to transport in exosomes. Changes in circulating miRNAs have been associated with several CeD associated immune-mediated diseases. The primary aim of this study is to identify circulating miRNAs that could function as CeD biomarkers, hopefully in the earliest stages of disease development and to identify miRNAs that could help monitoring the patient’s adherence to the gluten free diet. Methods: The prospective PreventCD study provides a unique cohort for CeD biomarker discovery. In this study blood was drawn from infants at high risk of CeD at set time points after birth, at time of CeD diagnosis and after start of the GFD. MiRNA profiles were determined in 192 serial samples of 49 PreventCD participants, of which 33 that developed CeD during the study. Total RNA was isolated from serum and miRNAs were sequenced by next generation sequencing. After quality control, the DESeq2 R-package was used to evaluate differential expression. Results After quality control, 97 samples were included in the differential expression analyses. Many miRNAs were significant (corrected for false discovery rate) in both the M4 versus DG and the Control versus CeD analyses. Intriguingly, five of these miRNAs (-205-5p, 203a, -1307-5p, -96-5p, 335-5p) seemed to start to normalize again at a GFD. Conclusion: Some of the miRNA candidates appear to be potential CeD biomarkers that can be detected before the increase in specific CeD antibody levels can be observed.

Item Type:	Thesis (Thesis)
Supervisor name:	Withoff, S. and Wijmenga, C.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 11:03
Last Modified:	25 Jun 2020 11:03
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/2272

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