Extracellular matrix remodeling genes polymorphisms and risk of chronic bronchitis and recurrent pneumonia in children

Abstract

We investigated the association of matrix metalloproteinases, the disintegrin and metalloprotease 33 and the tissue and serum inhibitors of proteinase gene polymorphisms with severe chronic respiratory diseases in Tatar children. We analyzed the case-control data sample from a total of 592 Tatar individuals, consisting of 119 children with chronic bronchitis, 138 with recurrent pneumonia and 335 control children residing in Ufa (Russia). The percentage of heterozygous genotype for the MMP9 (2660A>G) was higher among healthy children (52.54% vs 36.13% in chronic bronchitis patients, P-adj = 0.0033, P-cor = 0.033, odds ratio (OR) = 0.51; and 36.96% in recurrent pneumonia group, P-adj = 0.0034, P-cor = 0.034, OR = 0.53). The MMP12 (-82A>G) locus was associated with chronic bronchitis in the additive model (P-adj = 0.0091, P-cor = 0.09, OR = 0.45, beta = -0.798). The relationship between the 6A6A genotype of MMP3 (-1171 5A>6A) (P-adj = 0.0013, P-cor = 0.013, OR = 3.91) and the 6A-A haplotype of MMP3 (-1171 5A>6A) and MMP12 (-82A>G) and recurrent pneumonia were unraveled (P-adj = 0.001, P-cor = 0.01, OR = 2.07). This haplotype was also associated with a higher risk of chronic bronchitis (P-adj = 0.0012, P-cor = 0.012, OR = 2.15). The TIMP3 (-1296T>C) was associated with recurrent pneumonia in the dominant model (P-adj = 0.0031, P-cor = 0.031, OR = 1.91). The MMP9, MMP3 and TIMP3 (tissue inhibitors of matrix metalloproteinases) polymorphisms and MMP3 and MMP12 haplotypes may play a substantial role in susceptibility to severe airway and lung injury in children with chronic bronchitis and recurrent pneumonia.