-511C>T (rs16944) and +3953 C>T (rs1143634) Genotypes and Haplotypes of IL1B Gene and VNTR Polymorphism of IL1RN as Risk Factors for COPD

Background: COPD is a multifactorial chronic lung disease driven by an abnormal inflammatory reaction. It is well recognized that genetic factors play a role in susceptibility to COPD. Hence, polymorphism in pro-inflammatory cytokines, including interleukin-1 (IL-1), may confer a risk for the development of COPD. Methods: We genotyped 163 patients with COPD and 174 control individuals using a TaqMan genotyping assay for IL1B -511 C>T SNP and a PCR-RFLP-based method for IL1B +3953 C>T SNP and VNTR polymorphism in IL1RN in order to elucidate their possible role as candidate risk factors of COPD in a Bulgarian population. Results: The genotypes containing at least one variant T allele of IL1B -511 C>T SNP demonstrated a 2.1-fold higher risk for COPD after adjustment for age, sex, and smoking status (p = 0.011). The genotype with at least one T allele of IL1B +3953 C>T appeared to be protective, with a 2.21-fold lower risk for COPD after adjustment for sex, age, and smoking status (p = 0.007). The IL1B T_C haplotype showed a 1.70-fold higher risk of COPD (p = 0.018) in comparison to the C_T haplotype. Carriers of the VNTR IL1RN 1*3 genotype develop COPD earlier compared to 1*1 (p = 0.099). Patients with the 2*2 genotype had slightly higher FEV1/FVC (%) in comparison to 1*2 carriers (p = 0.09). Conclusions: To our knowledge, this study is the first to provide exploratory evidence on the T_C haplotype of IL1B -511 C>T; +3953 C>T that may be a predisposing factor for COPD in Bulgarian population. We suggest that the VNTR polymorphism of the IL1RN gene does not affect the risk for COPD but may lead to early disease development.