Association of autophagy related gene polymorphisms with neutrophilic airway inflammation in adult asthma
Association of autophagy related gene polymorphisms with neutrophilic airway inflammation in adult asthma
Background/aims: role of autophagy in neutrophil function and the association of autophagy and autophagy related (ATG) gene polymorphisms with asthma susceptibility were suggested. In this study, we investigated the genetic association of ATG5 and ATG7 polymorphisms with asthma risk, severity and neutrophilic airway inflammation.
Methods: we recruited 408 asthma patients and 201 healthy controls. Sputum neutrophil counts were determined by H&E staining. Serum interleukin 8 (IL-8) levels were measured by enzyme-linked immunosorbent assay (ELISA). Genetic polymorphisms of ATG5 (-769T>C, -335G>A, and 8830C>T) and ATG7 (-100A>G and 25108G>C) were genotyped. The functional activities of ATG5 -769T>C and -335G>A variants were investigated by luciferase reporter assays.
Results: no associations of ATG5 and ATG7 polymorphisms with asthma susceptibility and severity were found. ATG5 -769T>C and -335G>A were in complete linkage disequilibrium. In the asthma group, GA/AA genotypes at ATG5 -335G>A were associated with higher neutrophil counts in sputum (p < 0.05); CC/TT genotype at ATG5 8830C>T associated with lower FEV1% predicted value (p < 0.05). DNA fragments containing ATG5 -769T and -335G alleles had higher promoter activities compared to those with -769C and -335A in both human airway epithelial cells (A549, p < 0.01) and human mast cell (HMC-1, p < 0.001). GG and CC genotype at ATG7 -100A>G and 25108G>C were significantly associated with high serum levels of IL-8 (p < 0.05 for both variants).
Conclusions: genetic polymorphisms of ATG5 and ATG7 could contribute to neutrophilic airway inflammation in the pathogenesis of adult asthma.
Adolescent, Adult, Asthma/blood, Autophagy/genetics, Autophagy-Related Protein 5/genetics, Autophagy-Related Protein 7/genetics, Case-Control Studies, Cell Line, Female, Gene Frequency, Genes, Reporter, Genetic Predisposition to Disease, Haplotypes, Heterozygote, Homozygote, Humans, Interleukin-8/blood, Male, Middle Aged, Neutrophil Infiltration/genetics, Neutrophils/immunology, Phenotype, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Risk Factors, Severity of Illness Index, Transfection, Young Adult
375-85
Pham, Duy Le
4e852cde-fcf8-4291-9138-c28fcf22bcb9
Kim, Seung-Hyun
1412648d-b752-4da5-8b03-8a37cc2f00b2
Losol, Purevsuren
13912f45-98d6-4aba-b057-0027993de4c7
Yang, Eun-Mi
70cb0f6f-2957-4146-8078-3ff9ff2a2e3f
Shin, Yoo Seob
42b5e5df-f5f5-4b75-9993-7a7447e76b43
Ye, Young-Min
8270ed6d-1696-48b9-a3d9-84f931341422
Park, Hae-Sim
00bcb025-0437-4185-a733-d2c935a3945b
March 2016
Pham, Duy Le
4e852cde-fcf8-4291-9138-c28fcf22bcb9
Kim, Seung-Hyun
1412648d-b752-4da5-8b03-8a37cc2f00b2
Losol, Purevsuren
13912f45-98d6-4aba-b057-0027993de4c7
Yang, Eun-Mi
70cb0f6f-2957-4146-8078-3ff9ff2a2e3f
Shin, Yoo Seob
42b5e5df-f5f5-4b75-9993-7a7447e76b43
Ye, Young-Min
8270ed6d-1696-48b9-a3d9-84f931341422
Park, Hae-Sim
00bcb025-0437-4185-a733-d2c935a3945b
Pham, Duy Le, Kim, Seung-Hyun, Losol, Purevsuren, Yang, Eun-Mi, Shin, Yoo Seob, Ye, Young-Min and Park, Hae-Sim
(2016)
Association of autophagy related gene polymorphisms with neutrophilic airway inflammation in adult asthma.
The Korean journal of internal medicine, 31 (2), .
(doi:10.3904/kjim.2014.390).
Abstract
Background/aims: role of autophagy in neutrophil function and the association of autophagy and autophagy related (ATG) gene polymorphisms with asthma susceptibility were suggested. In this study, we investigated the genetic association of ATG5 and ATG7 polymorphisms with asthma risk, severity and neutrophilic airway inflammation.
Methods: we recruited 408 asthma patients and 201 healthy controls. Sputum neutrophil counts were determined by H&E staining. Serum interleukin 8 (IL-8) levels were measured by enzyme-linked immunosorbent assay (ELISA). Genetic polymorphisms of ATG5 (-769T>C, -335G>A, and 8830C>T) and ATG7 (-100A>G and 25108G>C) were genotyped. The functional activities of ATG5 -769T>C and -335G>A variants were investigated by luciferase reporter assays.
Results: no associations of ATG5 and ATG7 polymorphisms with asthma susceptibility and severity were found. ATG5 -769T>C and -335G>A were in complete linkage disequilibrium. In the asthma group, GA/AA genotypes at ATG5 -335G>A were associated with higher neutrophil counts in sputum (p < 0.05); CC/TT genotype at ATG5 8830C>T associated with lower FEV1% predicted value (p < 0.05). DNA fragments containing ATG5 -769T and -335G alleles had higher promoter activities compared to those with -769C and -335A in both human airway epithelial cells (A549, p < 0.01) and human mast cell (HMC-1, p < 0.001). GG and CC genotype at ATG7 -100A>G and 25108G>C were significantly associated with high serum levels of IL-8 (p < 0.05 for both variants).
Conclusions: genetic polymorphisms of ATG5 and ATG7 could contribute to neutrophilic airway inflammation in the pathogenesis of adult asthma.
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kjim-2014-390
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More information
Accepted/In Press date: 17 August 2015
e-pub ahead of print date: 23 December 2015
Published date: March 2016
Keywords:
Adolescent, Adult, Asthma/blood, Autophagy/genetics, Autophagy-Related Protein 5/genetics, Autophagy-Related Protein 7/genetics, Case-Control Studies, Cell Line, Female, Gene Frequency, Genes, Reporter, Genetic Predisposition to Disease, Haplotypes, Heterozygote, Homozygote, Humans, Interleukin-8/blood, Male, Middle Aged, Neutrophil Infiltration/genetics, Neutrophils/immunology, Phenotype, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Risk Factors, Severity of Illness Index, Transfection, Young Adult
Identifiers
Local EPrints ID: 507151
URI: http://eprints.soton.ac.uk/id/eprint/507151
ISSN: 1226-3303
PURE UUID: ad690455-7218-4c70-b25f-a87126a4961a
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Date deposited: 28 Nov 2025 17:31
Last modified: 29 Nov 2025 03:07
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Contributors
Author:
Duy Le Pham
Author:
Seung-Hyun Kim
Author:
Purevsuren Losol
Author:
Eun-Mi Yang
Author:
Yoo Seob Shin
Author:
Young-Min Ye
Author:
Hae-Sim Park
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