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Genetic variants in IL17A and serum levels of IL-17A are associated with COPD related to tobacco smoking and biomass burning.

ABSTRACT: IL-17A is an important pro-inflammatory cytokine involved in the inflammatory response in chronic obstructive pulmonary disease (COPD). To evaluate the role played by single nucleotide polymorphisms of IL17A and protein levels in susceptibility to COPD, 1,807 subjects were included in a case-control study; 436 had COPD related to tobacco smoking (COPD-S) and 190 had COPD related to biomass burning (COPD-BB). Six hundred fifty-seven smokers without COPD (SWOC) and 183 biomass burning-exposed subjects (BBES) served as the respective control groups. The CC genotype and C allele of rs8193036 were associated with COPD (COPD-S vs. SWOC: p?

SUBMITTER: Ponce-Gallegos MA

PROVIDER: S-EPMC6972744 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Genetic variants in IL17A and serum levels of IL-17A are associated with COPD related to tobacco smoking and biomass burning.

Ponce-Gallegos Marco A MA Pérez-Rubio Gloria G Ambrocio-Ortiz Enrique E Partida-Zavala Neftali N Hernández-Zenteno Rafael R Flores-Trujillo Fernando F García-Gómez Leonor L Hernández-Pérez Andrea A Ramírez-Venegas Alejandra A Falfán-Valencia Ramcés R

Scientific reports 20200121 1

IL-17A is an important pro-inflammatory cytokine involved in the inflammatory response in chronic obstructive pulmonary disease (COPD). To evaluate the role played by single nucleotide polymorphisms of IL17A and protein levels in susceptibility to COPD, 1,807 subjects were included in a case-control study; 436 had COPD related to tobacco smoking (COPD-S) and 190 had COPD related to biomass burning (COPD-BB). Six hundred fifty-seven smokers without COPD (SWOC) and 183 biomass burning-exposed subj ...[more]

PMID: 31964947

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Project description:Heat shock proteins (HSP) genes are a superfamily responsible for encoding highly conserved proteins that are important for antigen presentation, immune response regulation, and cellular housekeeping processes. These proteins can be increased by cellular stress related to pollution, for example, smoke from biomass burning and/or tobacco smoking. Single nucleotide polymorphisms (SNPs) in these genes could affect the levels of their proteins, as well as the susceptibility to developing lung diseases, such as chronic obstructive pulmonary disease (COPD), related to the exposure to environmental factors. Methods: The subjects included were organized into two comparison groups: 1,103 smokers (COPD patients, COPD-S = 360; smokers without COPD, SWOC = 743) and 442 never-smokers who were chronically exposed to biomass smoke (COPD patients, COPD-BS = 244; exposed without COPD, BBES = 198). Eight SNPs in three HSP genes were selected and genotyped: four in HSPA1A, two in HSPA1B, and two in HSPA1L. Sputum expectoration was induced to obtain pulmonary cells and relative quantification of mRNA expression. Subsequently, the intracellular protein levels of total Hsp27, phosphorylated Hsp27 (Hsp27p), Hsp60, and Hsp70 were measured in a sample of 148 individuals selected based on genotypes. Results: In the smokers' group, by a dominant model analysis, we found associations between rs1008438 (CA+AA; p = 0.006, OR = 1.52), rs6457452 (CT+TT; p = 0.000015, OR = 1.99), and rs2763979 (CT+TT; p = 0.007, OR = 1.60) and the risk to COPD. Among those exposed to biomass-burning smoke, only rs1008438 (CA+AA; p < 0.01, OR = 2.84) was associated. Additionally, rs1008438 was associated with disease severity in the COPD-S group (AA; p = 0.02, OR = 2.09). An increase in the relative expression level of HSPA1A was found (12-fold change) in the COPD-BS over the BBES group. Differences in Hsp27 and Hsp60 proteins levels were found (p < 0.05) in the comparison of COPD-S vs. SWOC. Among biomass-burning smoke-exposed subjects, differences in the levels of all proteins (p < 0.05) were detected. Conclusion: SNPs in HSP genes are associated with the risk of COPD and severe forms of the disease. Differences in the intracellular Hsp levels are altered depending on the exposition source.

Project description:Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease that mainly affects the axial and sacroiliac joints. Single-nucleotide polymorphisms (SNPs) in genes encoding cytokines have been associated with AS, which can interfere with the production of these cytokines and contribute to the development of AS. In order to contribute to a better understanding of the pathology of AS, our objective was to investigate a possible association of the IL10 -1082 A>G SNP (rs1800896) with AS and to evaluate the serum levels of TNF-α, IL-10, IL-17A, and IL-17F in AS patients and controls comparing them with their respective genotypes (TNF rs1800629, IL10 rs1800896, IL17A rs2275913, and IL17F rs763780). Patients and controls were selected from the Maringá University Hospital and the Maringá Rheumatism Clinic, in Paraná State, Southern Brazil, and they were diagnosed by the ASAS Criteria. In total, 149 patients and 169 controls were genotyped for the IL10 -1082 A>G polymorphism using a polymerase chain reaction with sequence specific primers (PCR-SSP); the measurement of TNF-α serum levels was performed through the immunofluorimetric test and IL-10, IL-17A, and IL-17F using an ELISA test. There was a high frequency of the IL10 -1082 G allele in AS patients compared with controls with an odds ratio of 1.83 and 95% confidence interval of 1.32 to 2.54, and a significant difference in the genotype frequencies of the IL10 -1082 A/G+G/G between patients and healthy controls, with an odds ratio of 3.01 and 95% confidence interval of 1.75 to 5.17. In addition, increased serum levels of IL-10 were observed in AS patients: 2.38 (IQR, 0.91) pg/ml compared with controls 1.72 (IQR 0.93) pg/ml (P = 0.01). Our results also showed an association between IL17F rs763780 C/T+T/T genotypes and increased serum levels of IL-17F in patients with AS and also in controls. We can conclude that patients with the A/G and G/G genotypes for -1082 A>G (rs1800896) in the IL10 gene are three times more likely to develop AS, that the serum level of IL-10 was higher in AS patients and that the IL17F rs763780 polymorphism can affect the levels of IL-17F in the serum of patients and controls in the same way.

Dataset Information

Genetic variants in IL17A and serum levels of IL-17A are associated with COPD related to tobacco smoking and biomass burning.

Publications

Genetic variants in IL17A and serum levels of IL-17A are associated with COPD related to tobacco smoking and biomass burning.

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