Genetic variants inTNFα,TGFB1, PTGS1andPTGS2genes are associated with diisocyanate-induced asthma

Abstract

Diisocyanates are the most common cause of occupational asthma, but risk factors are not well defined. A case-control study was conducted to investigate whether genetic variants in inflammatory response genes (TNFα, IL1α, IL1β, IL1RN, IL10, TGFB1, ADAM33, ALOX-5, PTGS1, PTGS2 and NAG-1/GDF15) are associated with increased susceptibility to diisocyanate asthma (DA). These genes were selected based on their role in asthmatic inflammatory processes and previously reported associations with asthma phenotypes. The main study population consisted of 237 Caucasian French Canadians from among a larger sample of 280 diisocyanate-exposed workers in two groups: workers with specific inhalation challenge (SIC) confirmed DA (DA+, n = 95) and asymptomatic exposed workers (AW, n = 142). Genotyping was performed on genomic DNA, using a 5′ nuclease PCR assay. After adjusting for potentially confounding variables of age, smoking status and duration of exposure, the PTGS1 rs5788 and TGFB1 rs1800469 single nucleotide polymorphisms (SNP) showed a protective effect under a dominant model (OR = 0.38; 95% CI = 0.17, 0.89 and OR = 0.38; 95% CI = 0.18, 0.74 respectively) while the TNFα rs1800629 SNP was associated with an increased risk of DA (OR = 2.08; 95% CI = 1.03, 4.17). Additionally, the PTGS2 rs20417 variant showed an association with increased risk of DA in a recessive genetic model (OR = 6.40; 95% CI = 1.06, 38.75).These results suggest that genetic variations in TNFα, TGFB1, PTGS1 and PTGS2 genes contribute to DA susceptibility.

Network Pharmacology Strategy to Investigate the Pharmacological Mechanism of HuangQiXiXin Decoction on Cough Variant Asthma and Evidence‐Based Medicine Approach Validation

“…Previous research has indicated that AKT1 is related to pathway mechanisms in children with severe asthma [ 33 ]; IL6 polymorphisms are related to the effects of smoking on the risk of adult asthma [ 34 ]; VEGFA rs833069 SNPs are associated with asthma [ 35 ]; VEGFA is associated with the response to inhaled corticosteroids in children with asthma [ 36 ]; smoking aggravates airway inflammation by activating the c -Jun amino terminal kinase pathway in asthma [ 37 ]; EGFR activation-induced decreases in claudin 1 promote MUC5AC expression and exacerbated asthma in mice [ 38 ]; the EGRF-dependent signaling pathway is associated with diseases, such as asthma [ 39 ]; neutrophils release CXCL8, NE, and MMP-9 in response to viral surrogates with R848-induced CXCL8 release being specifically enhanced in neutrophils in asthma [ 40 ]. CASP3 may play a role in allergic asthma [ 41 ]; the PTGS2 gene is associated with diisocyanate-induced asthma [ 42 ]. The relationships between these key targets and CVA, some of which have been well studied, could be further studied, and possible mechanisms that have not been previously studied could be explored.…”

Genetic variants with gene regulatory effects are associated with diisocyanate-induced asthma

“…11,12 Genetic association studies of diisocyanate-exposed workers, including 2 genome-wide association studies (GWASs), have identified DA-associated genetic variants from multiple loci, some reaching genome-wide significance. [13][14][15][16][17][18][19][20][21] A potential study limitation is the small number of workers with DA able to be recruited (a relatively rare disorder). In the latter publications 19,20 a very well-defined disease phenotype of OA confirmed by using controlled specific inhalation challenge (SIC) testing with the work-relevant isocyanate chemical could explain the large number of reported disease-associated single nucleotide polymorphisms (SNPs).…”

“…In the latter publications 19,20 a very well-defined disease phenotype of OA confirmed by using controlled specific inhalation challenge (SIC) testing with the work-relevant isocyanate chemical could explain the large number of reported disease-associated single nucleotide polymorphisms (SNPs). DA-associated SNPs have been found in genes encoding antioxidant enzymes, 13,21 HLA class I and II molecules, 18 T H 1/ T H 2 cytokines and CD14, 14,16 and epithelial junctional proteins. 22 Previously, we replicated DA associations with 2 CTNNA3 (a-T catenin) SNPs previously reported in a GWAS of Korean workers.…”

Changes of Innate Immunity Indexes in Severe Asthma in Children

“…подавляет аллергическое воспаление [10]. Однако в ряде работ показано повышение содержания и активности цитокина ТGF-β1 у больных БА, особенно после контакта с аллергеном, что ведет к увеличению количества воспалительных клеток в бронхах [18]. ТGF-β1 действует также на фибробласты, эндотелиальные клетки и гладкую мускулатуру дыхательных путей и способствует формированию ремоделирования дыхательных путей при БА [17].…”