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.