Association of polymorphic variants of matrix metalloproteinase and antiprotease genes with development and severity of chronic obstructive pulmonary disease

Abstract

To evaluate a role of polymorphic variants of metalloproteinase and protease genes for hereditary susceptibility to COPD and its severity, we analyzed polymorphic loci of MMP1, MMP9, MMP12, PI, and AACT genes in COPD patients (n = 318) and healthy persons (n = 319) living at the Bashkortostan Republic. Results showed that frequency of genotypes and alleles of G(-1607)GG gene MMP1, С(-1562)T gene MMP9, A(-82)G gene MMP12, and Ala 15 Thr gene ААСТ did not differ in COPD patients and healthy subjects. The Zand S-mutations of the PI gene were also similar in both the groups. The heterozygous GA genotype of G1237A locus in the 3'-non-translated region of PI gene was associated with COPD occurrence (OR = 2.09; 95 % CI: 1.15–3.81). To determine polymorphic variants associated with severity of clinical course and age of the disease manifestation, a comparative analysis of rates of genotypes and alleles was performed in patients with different COPD stages and of different age. The stage IV COPD patients significantly more often carried rare T allele in С(-1562)T locus of the MMP9 gene (15.89 % vs 8.38 %; χ² = 7.804; df = 1; p = 0.005; OR = 2.06; 95 % CI: 1.22–3.49). Individuals with rare TT genotype of MMP9 gene were found only among the stage IV COPD patients (3.97 % vs 0 %; χ² = 4.78; p = 0.029; p_cor = 0.058). Moreover, analysis of this locus in patients with early manifestation of COPD (younger the 55 yrs) revealed significantly more frequent rate of T allele in patients with stage IV COPD compared to patients of the same age but less severe COPD (χ² = 5.26; df = 1; p = 0.022).