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

• Published in: Respiratory medicine Vol. 185; p. 106462
• Main Authors: Chen, Liang, Lei, Yan, Zhang, Lingling
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2021
• Subjects: A549 Cells; C-X-C motif Chemokine ligand 14; Chemokines, CXC - genetics; Chemokines, CXC - metabolism; Chemokines, CXC - physiology; DNA methylation; DNA Methylation - genetics; Gene Expression - genetics; Gene Expression Regulation, Viral - genetics; Genotype; Humans; Influenza A; 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; Single nucleotide polymorphism; SNP genotyping; T-Lymphocytes - immunology; DNA methylation; Influenza A; Single nucleotide polymorphism; C-X-C motif Chemokine ligand 14; SNP genotyping
• ISSN: 0954-6111; 1532-3064; 1532-3064
• DOI: 10.1016/j.rmed.2021.106462

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. 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. 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. CXCL14 promoter region DNA methylation and SNP were correlated with H1N1 severity. •CXCL14 is downregulated in H1N1 patients.•CXCL14 is highly methylated in patients and A549 cells infected with H1N1.•CXCL14 methylation is related to the severity of H1N1.•GA and AA in CXCL14 are risk genotypes for H1N1; while AA for severe H1N1.•rs2547 of CXCL14 is related to the severity of H1N1.