Polymorphism in promoter regions of matrix metalloproteinases (MMP1, MMP9, and MMP12) in chronic obstructive pulmonary disease patients

Our studies have shown that the genotype and allele frequencies of polymorphisms G(-1607)GG of MMPI gene, C(-1562)T of MMP9 gene, and A(-82)G of MMP12 gene do not significantly differ in the samples of chronic obstructive pulmonary disease (COPD) patients (N = 318) and healthy controls (N = 319) dwellina in Bashkortostan Republic. However, association of (-1562)T allele of the MMP9 gene with the severity of COPD disease progression has been revealed. In COPD patients at stage 4 of the disease, the frequency of allele T was significantly higher that in patients with the stages 2 and 3 (15.89% versus 8.38%; chi(2) = 7.804; d.f. = 1; P = 0.005; OR = 2.06 95% CI 1.22-3.49). The distribution of the genotype frequencies of C(-1562)T polymorphism of MMP9 gene significantly differed between the patients with various COPD severity (chi(2) = 9.849; d.f = 2; P = 0.007). The individuals with rare genotype TT were revealed only among patients with severe COPD form (3.97% versus 0%; chi(2) = 4.78; P = 0.029; P-cor = 0.058). Analysis of this polymorphism in patients with early COPD onset (younger than 55 years old) has shown a significant increase in the allele T frequency in the group of patients with severe COPD (stage 4 according to GOLD) compared to the patients of the same age but with less severe COPD progression (chi(2) = 5.26; d.f. = 1; P = 0.022). As the major clinical characteristics of stage 4 COPD is the development of pulmonary emphysema as well as bronchial walls deformation, we suggest that the increased expression of MMP9 gene caused by genetic polymorphism in the gene promoter is important in the early development of serious complications of the disease.