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Structure and functional impact of seed region variant in MIR-499 gene family in bronchial asthma

Respiratory Research Sep 14, 2017

Toraih EA, et al. - This study was designed not only to investigate the role of microRNA-499 (MIR-499) gene family polymorphism as a marker for susceptibility and progression of bronchial asthma but also to analyze the structural and functional impact of rs3746444 within the seed region. On the basis of the data collected, it was concluded that miR-499 rs3746444 (A > G) polymorphism were related to asthma susceptibility and bronchodilator response in Egyptian children and adolescents.

Methods

  • For this study, genotyping for one hundred ninety-two members (96 patients and 96 controls) in the discovery phase and 319 subjects (115 patients and 204 controls) in the replication phase was performed by means of Real Time-Polymerase Chain Reaction technology.
  • After that, patients underwent the methacholine challenge test and biochemical analysis.
  • Gene structural and functional analysis, target prediction, annotation clustering, and pathway enrichment analysis were executed.
  • Predicted functional effect of rs37464443 SNP was explored.

Results

  • Researchers reported that miR-499 gene family is highly implicated in inflammation-related signaling pathways.
  • They suggested that Rs374644 (A > G) in MIR499A and MIR499B within the seed region could disrupt target genes and create new genes.
  • The G variant was related to high risk of developing asthma under all genetic association models (G versus A: OR = 3.27, 95% CI = 2.53–4.22; GG versus AA: OR = 9.52, 95% CI = 5.61–16.5; AG versus AA: OR = 2.13, 95% CI = 1.24–3.46; GG + AG versus AA: OR = 4.43, 95% CI = 2.88–6.82).
  • In addition, GG genotype was correlated with poor pre-bronchodilator FEV1 (p = 0.047) and the worst bronchodilator response after Salbutamol inhalation, represented in low peaked expiratory flow rate (p = 0.035).

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