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, β=-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 (Padj=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.

MMP‐3 (–1171 5A/6A; Lys45Glu) variants affect serum levels of matrix metalloproteinase (MMP)‐3 and correlate with severity of COPD: A study of MMP‐3, MMP‐7 and MMP‐12 in a Tunisian population

“…indicating that the (–82) G allele associates with a reduced risk of COPD. The results of the present study also disagree with those of Korytina et al . who found a significant association between the (–82) A/G variant and increased risk of chronic bronchitis.…”

“…and Tacheva et al30 indicating that the (-82) G allele associates with a reduced risk of COPD. The results of the present study also disagree with those of Korytina et al31 who found a significant association between the (-82) A/G variant and increased risk of chronic bronchitis. Likewise, data from studies by Haq et al32 and Arja et al33 showed an association between the (-82) A/357 A haplotype and the risk of developing COPD.…”

Predose and Postdose Blood Gene Expression Profiles Identify the Individuals Susceptible to Acetaminophen-Induced Liver Injury in Rats

“…Other MMPs also increased in the liver in response to carbon tetrachloride (CCl 4 ) administration, relating to inflammatory reactions [ 39 ], as well as APAP treatment, which were associated with hepatocellular damage and hepatic microcirculatory dysfunction [ 40 ]. Moreover, MMP12 haplotype may play a critical role in susceptibility to severe airway and lung injury in children with chronic bronchitis and recurrent pneumonia [ 41 ]. Therefore, we inferred that increased susceptibility to AILI in the rats with innately lower expression of Mmp12 might be the result of lacking tissue repair and remodeling ability to APAP-induced tissue damages.…”

Analysis of polymorphisms of genes associated with immune response and tissue remodeling in occupational chronic bronchitis

“…TIMP3 is located on chro mosome 22 at site 22q12.1 q13.2; the (-1296T>C) polymorphisms in the gene promoter is thought to affect the level of TIMP3 transcription [13]. It was reported that TIMP3 contributes to the resolution of acute inflammatory damage to lung tissue [41]; the data from our previous studies suggested that TIMP3 locus was associated with COPD and with lingering childhood pneumonia [15,42].…”