Analysis of polymorphisms of genes associated with immune response and tissue remodeling in occupational chronic bronchitis

The involvement of polymorphisms of genes encoding immune response-associated molecules (LTA, TNFA, IL1B, ILRN, IL8, IL10, VDBP), matrix metalloproteinases (MMP1, MMP2, MMP3, MMP9, MMP12, ADAM33), and tissue and serum inhibitors of metalloproteinases (TIMP2, TIMP3, SERPINA1, SERPINA3) in the predisposition to occupational chronic bronchitis was assessed by PCR-RFLP analysis in groups of patients (n = 122) and healthy workers (n = 166). It was found that occupational chronic bronchitis was associated with polymorphisms of VDBP (P_adj = 0.00005, OR_adj = 2.06), MMP1 (P_adj = 0.00002, OR_adj = 2.57), ADAM33 (P_adj = 0.0004, OR_adj = 2.52), and IL8 (P_adj = 0.0058, OR_adj = 2.87). The most significant association was observed for the VDBP polymorphism 1296T>G. The VDBP haplotype GC*1S by the loci 1296T>G and 1307C>A was an informative susceptibility marker (P_adj = 0.0001, OR_adj = 2.60, 95%CI (1.62–4.19)). There was also a significant interaction between the VDBP polymorphism 1307C>A and the duration of occupational exposure to hazardous factors (Pinteraction = 0.02). Apparently, the investigated polymorphisms of VDBP, MMP1, ADAM33, and IL8 contribute to the genetic susceptibility to chronic bronchitis induced by dust and toxic agents.