Role of -511C>T and +3953C>T SNPs of IL1B gene as risk factors of COPD and bronchial asthma in Bulgarian population

Abstract

A common characteristic of COPD and bronchial asthma is the chronic inflammation in the airways. In the current case-control study we investigated -511C>T promoter polymorphism and +3953C>T silent polymorphism of IL1B and their haplotypes as candidate risk factors of COPD and Bronchial asthma. We genotyped 163 patients with COPD, 47 with Bronchial asthma and 174 control individuals using Taqman genotyping assay for IL1B -511C>T and PCR-RFLP-based method for +3953C>T.

We did no observed significant differences in genotype frequencies of studied SNPs between controls and patients both with COPD and asthma, however the minor T allele of IL1B -511C>T was less frequently found in controls (0.305) than the patients with COPD (0.377, p=0.046) and especially with asthma (0.415, p=0.0002). The carriers of IL1B -511T allele (TT and TC genotypes) had 1.56-fold higher risk for development of COPD (p=0.045) and 2.25-fold higher risk of Bronchial asthma (p=0.019). The performed estimations of IL1B haplotypes showed that T_C haplotype (alleles found to determine enhanced expression of IL-1b), appeared to be associated with higher risk of COPD (OR=1.25, p=0.231) and asthma (OR=1.78, p=0.035) compared to the most common C_C haplotype and with 1.70-fold higher risk of COPD (p=0.018) and 1.37-fold higher risk of asthma (p=0.313) compared to the C_T haplotype, associated with lower IL1B expression.

We suggest that the -511C>T promoter SNP and +3953C>T silent polymorphisms in exon 5 of IL1B may influence the genetic predisposition of COPD and Bronchial asthma: the carriers of alleles and haplotypes supposed to define higher IL-1b levels are more susceptible for these diseases.