|
Vol 46(2012) N 3 p. 438-449; G.F. Korytina1*, O.S. Tselousova1,2, L.Z. Akhmadishina1, E.V. Viktorova3, S.Z. Zagidullin2, T.V. Viktorova1,2 Association of MMP3, MMP9, ADAM33, and TIMP3 Polymorphisms with Chronic Obstructive Pulmonary Disease and Its Progression 1Institute of Biochemistry and Genetics, Ufa Scientific Center, Russian Academy of Sciences, Ufa, 450054 Russia2Bashkir State Medical University, Ufa, 450000 Russia 3George-August University of Goettingen, Goettingen, Germany *guly_kory@mail.ru Received - 2011-09-30; Accepted - 2011-10-27 PCR-RFLP analysis was performed for 391 cases and 514 control individuals to analyze the contribution of polymorphisms of the matrix metalloproteinase genes MMP1 (-1607 G>GG, rs1799750; -519 A>G, rs494379), MMP2 (-735 C>T, rs2285053), MMP3 (-1171 5A>6A, rs35068180), MMP9 (-1562 C>T, rs3918242; 2660A>G, rs17576), MMP12 (-82 A>G, rs2276109), the disintegrin and metalloproteinase 33gene ADAM33 (12418 A>G, rs2280091; 13491 C>G, rs2787094), and tissue inhibitors of metalloproteinase genes TIMP2 (- 418 G>C, rs8179090) and TIMP3 (-1296 T>C, rs9619311) to chronic obstructive pulmonary disease. Significant association with increased rick of chronic obstructive pulmonary disease was observed for the 6A6A genotype of the MMP3 -1171 5A>6A polymorphism (OR = 2.49, Padj = 0.003979, Pcor= 0.0358 adjusted for age, sex, smoke pack-years, ethnicity) and for the G-G haplotype of ADAM33 polymorphisms 13491 C>G and 12418 A>G (OR = 0.39, Padj = 0.0012, Pcor = 0.006). Significant interactions were detected between the smoking status and ADAM33 12418 A >G (Pinteract = 0.026) and TIMP3 -1296 T>C (Pinteract = 0.044). The risk of emphysema was increased in GG homozygotes by ADAM33 13491 C>G and a risk of emphysema was found (OR = 1.74, Padj = 0.013, Pcor = 0.117). The severity of chronic obstructive pulmonary disease was modified by MMP9 -1562 C>T in the additive model (OR = 1.883, Padj = 0.028, Pcor = 0.252). Thus, polymorphisms of MMP3, MMP9, ADAM33, and TIMP3 can be considered important risk factors for the development and progression of chronic obstructive pulmonary disease; in addition, pathogenetically significant gene-environment interactions were identified. These data contribute to the understanding of hereditary predisposition to chronic obstructive pulmonary disease. chronic obstructive pulmonary disease, association, gene and environmental interactions, matrix metalloproteinases, disintegrin metalloproteinase, tissue inhibitors of metalloproteinases |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
