EPIGENETIC STUDY OF DNA METHYLATION IMPACT ON CHILDHOOD ASTHMA IN ZAGAZIG UNIVERSITY HOSPITALS | ||||
| Zagazig University Medical Journal | ||||
| Article 13, Volume 25, Issue 1, January 2019, Page 92-100 PDF (493.23 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/zumj.2019.23705 | ||||
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| Authors | ||||
| Dina Mohamed Shokry; Rabab Mohamed El-behedy; Amal Saeed Abd El-Azeem; Mona Hamed Hasanin Jehad | ||||
| Abstract | ||||
| Background: Asthma is the most common chronic inflammatory disorder of the airways in children, with rising incidence during last few decades which brings heavy burden to the whole society. The underlying molecular mechanisms leading to asthma remain largely unclear. In complex diseases such as asthma, DNA methylation offers a potential mechanism for environmental modification of genetic responses. Objective: Our study aimed to investigate the association of methylation at the ADRB2 promoter region with asthma development in Egyptian children and further effect on their level of asthma control. Subjects and methods: Our case control study included 80 children, distributed as two groups: 64 asthmatics as cases and another 16 healthy children as control group. The cases were further sub-divided into three sub-groups according the level of asthma control (based on GINA guidelines in 2015): 28 were well controlled asthmatics, 24 were partly controlled asthmatics and 12 patients were uncontrolled asthma. Blood-derived DNA samples from all children and assays of ADRB2 gene methylation was done using polymerase chain reaction. Pulmonary function testing, Skin prick testing and serum total IgE levels were measured using ELISA for all cases. Results: The DNA methylation at ADRB2 promoter gene was significantly higher in the asthmatic children than in non-asthmatic group. Moreover, it was also higher in uncontrolled group in comparison to partly controlled and uncontrolled groups. Our data revealed a significant relationship between methylated DNA in patients with positive skin prick test and those receiving steroid therapy. ROC analysis revealed that methylated DNA can excellently differentiate asthmatic patients from healthy controls with AUC of 0.84 for DNA methylation. The optimal sensitivity and specificity to differentiate asthmatic children from controls were (87.5% and 81.5% at a cutoff expression value >1). ROC analysis revealed that methylated DNA can differentiate uncontrolled or partially controlled asthmatic patients and controlled asthmatic patients with AUC of 0.891 for DNA methylation. The optimal sensitivity and specificity were (86.1% and 89.3% at a cutoff expression value >2.2). Conclusion: our study suggested that increased methylation at the ADRB2 promoter area is associated with increased asthma susceptibility and poor asthma control which put it as a possible diagnostic and prognostic biomarker for asthma assessment in the near future. | ||||
| Keywords | ||||
| Asthma; DNA Methylation; ADRB2 | ||||
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