Association Of GATA3-IL-13,IL-33-IL1RL1 Pathway Of Polymorphisms With Outdoor Air Pollution And Asthma

Asthma is a chronic inflammatory airway disease characterized by reversible airway obstruction,airway hyperresponsiveness,and chronic lung inflammation.In recent years,the incidence of asthma has been rising,especially in developing countries.It is estimated that the prevalence of asthma in the world reaches more than 300 million people.People gradually realize that asthma has brought a heavy economic burden on individuals,families,and society.The main causes of the disease are heredity and environmental factors.This article focuses on biomarkers,genetic polymorphisms,and outdoor environmental pollutants in Xinjiang.From March 2016 to March 2017,551 people were selected for the study in the Pediatrics,Respiratory,and Hospital Health Examination Centers.A total of 277 health groups were recruited at the Hospital Health Examination Center.A total of 274 cases and 277controls consisted of case-control studies.In the case-control group,there were 180 cases of asthma in children,174 cases of children’s health,94 cases of adult asthma,and 103cases of adult health.The effects of other respiratory diseases were excluded.The collected serum was tested for IL-13 and IL-33 levels by ELISA;DNA was extracted from the blood by the kit and amplified by PCR,and the bases of the gene locus were detected by time-of-flight mass spectrometry;Shihezi Environmental Monitoring Station obtained monthly average concentration of environmental pollutants from March 2016 to March 2017.The monitored environmental pollutants include:PM₁₀,PM_2.5,SO₂,and NO₂.One-way ANOVA was used to analyze the relationship between serum levels of IL-13,IL-33 and asthma.Multivariate unconditional logistic regression was used to analyze the correlation between serum factors,genes,outdoor environmental pollutants,asthmatic patients and in order to analyze the influence of gene-environment interactions on asthmatic patients.In this experiment,the results of ELISA detection of serum IL-13,IL-33 levels in children and adults showed that IL-13,IL-33 as pro-inflammatory factors involved in the incidence of asthma;The concentration of IL-33 and serum IL-13 in the case group was significantly higher than that in the healthy group;the serum levels of IL-13 in the GATA3rs3781093 locus CC genotype were higher than those in the CT and TT genotypes（35.02±34.38 pg/ml,27.23±24.03 pg/ml,26.90±29.84 pg/ml）.There was no statistically significant difference between the three groups P>0.05;IL-13 levels in the IL-13 gene rs2066960 AA genotype were higher than those in CC and AC genotypes（46.12±24.96 pg/ml,14.02±9.92 pg/ml,32.46±32.82 pg/ml）.The three groups were statistically significant（P<0.05）.The C-A mutation may affect the expression of IL-13;the IL-33 content in serum of the rs16924159 AA genotype of the IL-33 locus was higher than that of the AG.The GG genotype and the three groups were statistically significant（P<0.05）.The rs16924159 gene mutation in asthma patients may control the increase of IL-33;the IL-13 content in serum of the IL1RL1 gene rs1946131 CC genotype was higher than The TC and TT genotypes that were not statistically significant between the three groups（P>0.05）.To explore the correlation between GATA3,IL-13,IL-33,and IL1RL1 polymorphisms in children and adults in Xinjiang and the susceptibility of asthma in children and adults.The results showed that all five allele frequencies were consistent H-W balance except for five gene loci;Children with GATA3,IL-13,IL-33,IL1RL1 gene IL-33（rs16924159）genotype frequency distribution in the case and the control group there is a significant difference;gene locus asthma GATA3 gene rs3781093.There was no statistical significance between the genotypes and there was no significant difference in genotype and allele frequency distributions among the other 18 gene loci.The GATA3,IL-13,IL-33,IL1RL1 genotypes and their frequency distribution were not statistically significant in adults.The CC genotype of the GATA3 locus in the rs3781093 asthmatic group may be associated with the risk of asthma.The rs2066960 allele of IL-13 may increase the risk of asthma;genes in the rs16924159 and rs1420102 loci may increase the risk of asthma.The results of gene polymorphism,correlation between outdoor air pollution and asthma showed that the average concentrations of four pollutants PM_2.5,PM₁₀,SO₂ and NO₂ were70.5μg/m³,117.7μg/m³,and 14.7μg/m³,respectively,41.6μg/m³;concentration range were15.4-17.97.3μg/m³,44.1-283.8μg/m³,7.5-26.7μg/m³,26.0-89.9μg/m³;over-standard rate were 60.5%,58.4%,0,respectively.0.7%;multiple linear regression analysis using SPSS statistical software found that the exposure of two pollutants PM_2.5,NO₂ may be a risk factor for asthma patients;the genotype of rs3781093 in children was significantly different from the interaction of PM_2.5,PM₁₀,SO₂,and NO₂;the genotype of adult susceptibility locus rs3781093 was contaminated with PM_2.5,SO₂,and NO₂.There was no significant difference in the interactions;the interactive interaction between GATA3（rs3781093）genotypes seems to be more susceptible to asthma in children than that in adults.This study based on association of gene polymorphisms and outdoor environment pollution with asthma,screening for genetic susceptibility sites that increase the risk of asthma.To explore the impact of gene mutation sites on the expression of interleukins,effects of outdoor air pollutants and gene-environment interactions on asthma.The results of the study will provide scientific support and theoretical basis for the prevention and treatment of asthma in typical regions of Xinjiang.