Abstract
COPD is widespread airways disease of multifactorial nature. It is well known that geneteic factors play significant role in COPD pathogenesis. Infection is one of important COPD exogenous etiological factors. Previous study did not detected association of NRAMP1 gene polymorphisms with COPD development. Nevertheless we supposed that this COPD candidate gene may play role in COPD clinical signs Study objectives: To inverstigate the association of D543N, 1465-85G/A and 469+14G/C polymorphisms of NRAMP1 gene with COPD clinical presentation. Materials and methods: We examined 122 COPD patients (mean age 57±12). Average duration of disease is 17±12. DNA was extracted from venous blood. Polymorphisms were detected by polymerase chain reaction followed by restriction digestion. Results: The linkage of age of disease onset with 1465-85G/A polymorphisms of NRAMP1 gene was proved: mean age of disease onset is 34 and is associated with GG genotype, while GA and AA genotypes are associated with latest manifestation–at 43 (p=0,022). D543N polymorphisms are associated with modification of proteases inhibitors α1 PI and α2 MG activity in sputum. Carriers of homo-and heterozygote A allele of NRAMP1 gene condition have reliable decrease of α2 MG activity in sputum during exacerbation and increase of α1 PI in sputum during remission as compared with GG genotype carriers. Carriers of GC and CC genotypes of 469-14G/C polymorphic variant of NRAMP1 gene have increase of α1 PI activity in serum during COPD exacerbation (p Conclusion: Time of COPD manifestation is determined of 1465-85G/A polymorphisms of NRAMP1 gene. Inhibitors of proteases activity is determined of D543N and 469-14G/C polymorphisms of this gene.
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