[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.
G F
GF
Korytina
O S
OS
Tselousova
L Z
LZ
Akhmadishina
E V
EV
Victorova
Sh Z
ShZ
Zagidullin
T V
TV
Victorova
D051722:ADAM Proteins / Q000235:genetics*; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D005006:Ethnicity; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D012307:Risk Factors; D012426:Russia / Q000453:epidemiology; D012720:Severity of Illness Index; D012907:Smoking; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*
D015415:Biomarkers; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D051722:ADAM Proteins; C450441:ADAM33 protein, human; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9