Bioinformatics Analysis of Chronic Obstructive Pulmonary Disease (COPD)- Associated Interleukin-6 and CHRNA3 Genetic Variations
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Abstract
Background: Chronic Obstructive Pulmonary Disease (COPD) is the fourth leading cause of death in the world. Genetics factors were found to contribute in the aetiology and progression of COPD. Recent studies demonstrated a significant association of Interleukin-6 (IL-6) and Cholinergic Receptor Nicotinic Alpha 3 (CHRNA3) genetic variants with increased risk of COPD in large case-control cohort. In-silico analysis showed that a Single Nucleotide Polymorphism (SNP) rs1818879 is located in the 3’untranslated region (3’UTR) of IL-6 gene and a synonymous SNP rs1051730 positioned in exon 7 of CHRNA3 gene.
Objective: This report aims to use the available bioinformatics approach to investigate the potential functional effects of these COPD-related variants on the expression of IL-6 and CHRNA3 gene.
Materials and Methods: Bioinformatics analysis of the IL-6 3’UTR SNP (rs1818879) using miRBase software was conducted to predict the micro-RNA (miRNA) binding to the target sequence. The possible impact of CHRNA3 silent SNP (rs1051730) on RNA secondary structure was evaluated using Mfold software.
Results: Our analysis showed that the alternative allele of SNP rs1818879 in ‘3UTR of IL-6 could disrupt the binding site of miRNA (mir-619-5p). With regard to CHRNA3 exon 7 SNP (rs1051730), the single nucleotide change at this location was predicted to cause a significant variation in the secondary structure of CHRNA3 protein-coding transcripts.
Conclusion: The current study highlighted the possible role of regulatory and silent single nucleotide polymorphisms in disease pathogenesis. An extension of our work will include experimental validation using functional analysis.
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