Role of C-X-C motif chemokine ligand 14 promoter region DNA methylation and single nucleotide polymorphism in influenza A severity

Respir Med. 2021 Aug-Sep:185:106462. doi: 10.1016/j.rmed.2021.106462. Epub 2021 May 18.

Abstract

Objective: The purpose of our experiment is to discuss the function of DNA methylation and single nucleotide polymorphism (SNP) in C-X-C motif chemokine ligand 14 (CXCL14) promoter region in influenza A (H1N1) severity.

Methods: Clinic data and blood samples from H1N1 patients were collected. Blood routine indexes were measured. Levels of T lymphocytes were assessed. Importantly, CXCL14 expression and methylation in H1N1 patients and A549 cells were detected through functional assays. Additionally, rs2237061, rs2237062 and rs2547 of CXCL14 were genotyped to analyze the relation of CXCL14 SNP and H1N1 severity.

Results: The number of leukocytes, neutrophils and lymphocytes as well as T lymphocytes in H1N1 patients was lower than that in healthy subjects, and that was decreased in severe H1N1 patients compared with the mild H1N1 patients. In HIN1 patients, CXCL14 expression was decreased, while CXCL14 methylation was increased, and CXCL14 expression was further decreased and CXCL14 methylation was further increased in severe H1N1 patients. CXCL14 methylation was negatively correlated with T lymphocytes in H1N1 patients. CXCL14 methylation was elevated in H1N1-infected A549 cells. GA and AA genotypes of rs2547 in CXCL14 were risky genotypes for H1N1, and AA genotype was risky genotype for severe H1N1. Number of T lymphocytes was lower in H1N1 patients carrying AA genotype of rs2547 than that in GA + GG genotype.

Conclusion: CXCL14 promoter region DNA methylation and SNP were correlated with H1N1 severity.

Keywords: C-X-C motif Chemokine ligand 14; DNA methylation; Influenza A; SNP genotyping; Single nucleotide polymorphism.

MeSH terms

  • A549 Cells
  • Chemokines, CXC / genetics*
  • Chemokines, CXC / metabolism
  • Chemokines, CXC / physiology
  • DNA Methylation / genetics*
  • Gene Expression / genetics
  • Gene Expression Regulation, Viral / genetics*
  • Genotype
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics*
  • Influenza, Human / genetics*
  • Influenza, Human / immunology
  • Influenza, Human / virology*
  • Ligands
  • Lymphocyte Count
  • Patient Acuity*
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics*
  • T-Lymphocytes / immunology

Substances

  • CXCL14 protein, human
  • Chemokines, CXC
  • Ligands