[Association of the MMP3, MMP9, ADAM33 and TIMP3 genes polymorphic markers with development and progression of chronic obstructive pulmonary disease].

The contribution of the polymorphic markers of the matrix metalloproteinases MMP1 (-1607G > GG, rs1799750; -519A > G, rs494379), MMP2 (-735C > T, rs2285053), MMP3 (-1171 5A > 6A, rs35068180), MMP9 (-1562C > T, rs3918242; 2660A > G, rs17576), MMP12 (-82A > G, rs2276109), the disintegrin and metalloprotease 33 ADAM33 (12418A > G, rs2280091; 13491C > G, rs2787094), the tissue inhibitors of metalloproteinases TIMP2 (-418G > C, rs8179090), TIMP3 (-1296T > C, rs9619311) genes to chronic obstructive pulmonary disease has been assessed. For this purpose, PCR-RFLP analysis of the gene polymorphisms in case (N = 391) and control (N = 514) groups has been performed. The 6A6A genotype of the MMP3--1171 5A > 6A polymorphism was associated with significantly high risk of chronic obstructive pulmonary disease (OR = 2.490, Padj = 0.003979, Pcor = 0.0358 adjusted for age, sex, smoke pack-years, ethnos). Analysis showed an association of the G-G haplotype of 13491C > G and 12418A > G ADAM33 gene polymorphisms (OR = 0.39, Padj = 0.0012, Pcor = 0.006)with chronic obstructive pulmonary disease. We found a significant interaction of the smoking status and ADAM33 12418A > G (Pinteraction = 0.026) and TIMP3--1296T > C (Pinteraction = 0.044). The relationship between the GG genotype of the ADAM33 13491C > G and emphysema risk was found (OR = 1.74, Padj = 0.013, Pcor = 0.117). Severity of chronic obstructive pulmonary disease was modified by MMP9 -1562C > T in additive model (OR = 1.883, Padj = 0.028, Pcor = 0.252). The MMP3, MMP9, ADAM33, TIMP3 genes polymorphism may be an important risk factor for the development and progression of chronic obstructive pulmonary disease, important gene and environmental interactions were determined.

[Polymorphism of the genes for antioxidant defense enzymes and their association with the development of chronic obstructive pulmonary disease in the population of Bashkortostan].

In this study, frequencies of the polymorphic variants of the genes encoding antioxidant enzymes, GSTM1, GSTT1, GSTP1, CAT, GPX1, NQO1, SOD1, and SOD3 were examined in three ethnic groups of healthy subjects from the Republic of Bashkortostan (Russians, Tatars, and Bashkirs). An association of these markers with the development of chronic obstructive pulmonary disease (COPD) was tested. Interethnic differences relative to the distribution of the polymorphic variants of the GSTP1 locus Ile105Val and the NQO1 locus 609C/T were revealed. Relative to the genotype distribution at the Ile 105Val locus of the GSTP1 gene, ethnic group of Bashkirs was found to be statistically significantly different from Tatars (chi2 = 8.819; d.f. = 2; P = 0.012). Relative to the genotype frequency distribution pattern at the NQO1 locus 609C/T, the group of Bashkirs differed from Russians (chi2 = 8.913; df. = 2; P = 0.012). An association of genotype Val/Val of the GSTP1 Ile105Val locus with the risk of COPD in Russians (chi2 = 5.25; P = 0.022; Pcor = 0.044; OR = 4.09), and of the GSTP1 haplotype *D in Tatars, was demonstrated (chi2 = 11.575; P = 0.0014; Pcor = 0.0042; OR = 3.178). Genotype TT of the CAT -262C/T locus marked resistance to the COPD development in Russians (chi2 = 6.82; P = 0.0098; Pcor = = 0.0196; OR = 0.31; 95% CI, 0.119 to 0.77). The risk for COPD in the ethnic group of Tatars was associated with the CAT haplotype (-262)C(1167)T (chi2 = 6.038; P = 0.0147; Pcor = 0.044; OR = 1.71). Analysis of the NQO1 haplotypes at the 465C/T and6009C/T loci showed that haplotype 465C/609T was associated with COPD in Russians (chi2 = 4.571; P = 0.0328; Pcor = 0.01; OR = 1.799). It was demonstrated that Gly allele of the Arg213Gly polymorphic locus of the SOD3 gene marked the risk for COPD in the ethnic group of Tatars (OR = 2.23; 95% CI, 1.22 to 4.1). Thus, GSTP1, CAT, NQO1, and SOD3 polymorphisms play an important role in the development of COPD among the population of Bashkortostan.