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ABSTRACT
Bronchial asthma is a common chronic lung disease that is driven by abnormal inflammatory reactions in the airways in response to the complex interaction between genetics and environmental factors. The underlying inflammation in asthma is manifested by prominent eosinophil infiltration and Th2 inflammatory mediators; however the pro-inflammatory cytokines, particularly IL-1β, have also been found in increased amount in the sputum and BAL in individuals with bronchial asthma, especially in more severe state. Therefore, IL-1β is considered to be of importance in pathogenesis of this condition as the protein level of the cytokine is finely regulated by variety of factors, including genetics. The IL1B gene displays many SNPs both in promoter and coding regions, which have been associated with IL-1β production.
In the current case-control study we investigated -511C>T (rs16944) promoter polymorphism and +3953C>T (rs1143634) silent polymorphism in exon 5 of IL1B and their haplotypes as candidate risk factors of Bronchial asthma in Bulgarian population.
We genotyped 47 patients with bronchial asthma and 174 control individuals using Taqman genotyping assay for IL1B -511C>T SNP and PCR-RFLP-based method for +3953C>TSNP.
We did not observe statistically significant differences in genotype frequencies of IL1B -511C>T and IL1B +3953C>T between controls and patients with asthma (p=0.065 and p=0.987). However, the minor T allele of IL1B -511C>T was less frequently found in the controls (0.305) compared to the patients with asthma (0.415, p=0.0002). Carriers of IL1B -511T allele (TT or TC genotypes) appeared to have 2.25-fold higher risk for Bronchial asthma (95% CI: 1.127–4.498, p=0.019). The performed estimations of IL1B haplotypes did not reveal any difference in the haplotype frequencies between controls and patients with asthma (p=0.270). However, the T_C haplotype, constructed by alleles found to determine enhanced expression of IL-1β, appeared to be associated with higher risk of asthma (OR 1.78, 1.04–3.03, p=0.035) compared to the most common C_C haplotype.
Based on the results of the current study we suggest that the -511C>T promoter polymorphism and +3953C>T silent polymorphism in exon 5 of IL1B may influence the genetic predisposition of Bronchial asthma in Bulgarian population, as the carriers of alleles and haplotypes supposed to define higher IL-1β protein levels are more susceptible for this lung diseases.