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The selected genetic polymorphisms of metalloproteinases MMP2, 7, 9 and MMP inhibitor TIMP2 in sarcoidosis.

Piotrowski WJ, Górski P, Pietras T, Fendler W, Szemraj J - Med. Sci. Monit. (2011)

Bottom Line: MMPs and TIMP2 mRNA were measured in peripheral blood lysate using real-time RT-PCR.DNA for genetic polymorphism was extracted from peripheral blood by GTC method.No differences were found between TT and AT/AA patients in terms of radiological stage, lung function test parameters, activity markers and the presence/absence of Löfgren syndrome.

View Article: PubMed Central - PubMed

Affiliation: Division of Pneumology and Allergy, Medical University of Lodz, Lodz, Poland.

ABSTRACT

Background: Increased activity of metalloproteinases may play a role in the initiation and propagation of inflammation in sarcoidosis, and may also be one of the factors responsible for the development of lung fibrosis. The aim of this study was to verify whether polymorphisms of MMP2 C-735T, MMP7 A-181G, MMP9 T-1702A and tissue inhibitor of metalloproteinase (TIMP)2 G-418C predispose to sarcoidosis.

Material/methods: The study included 139 patients with sarcoidosis and 100 healthy subjects. MMPs and TIMP2 mRNA were measured in peripheral blood lysate using real-time RT-PCR. DNA for genetic polymorphism was extracted from peripheral blood by GTC method. Protein concentrations in peripheral blood lysates were measured by ELISA, and MMP2 and 9 activities in BAL fluid were estimated by gel zymography.

Results: TT genotype in MMP9 T-1702A was more frequent in sarcoidosis (p<0.0001, OR = 13.71, 95% CI 7.02-26.80) and resulted in higher expression of MMP9 mRNA (p<0.0001). No differences were found between TT and AT/AA patients in terms of radiological stage, lung function test parameters, activity markers and the presence/absence of Löfgren syndrome. There were no differences in the distribution of MMP2, MMP7 and TIMP2 polymorphisms. Messenger RNAs, as well as protein concentrations of MMP2, 7, 9, and TIMP2 were elevated in patients with sarcoidosis (p<0.0001 for each).

Conclusions: The TT homozygotes of MMP9 T-1702A genotype may be predisposed to sarcoidosis. Elevated MMP2, 7, 9, and TIMP2 mRNAs suggest their inducibility.

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Related in: MedlinePlus

Expression of mRNA in peripheral blood lysates of sarcoid patients with various MMPs/TIMP2 polymorphisms. Horizontal lines show mean values: (A) MMP2 C-735T (CC vs. CT vs. TT); (B) MMP7 A-181G (AA vs. AG vs. GG); (C) MMP9 T-1702A (TT vs. AT and AA); (D) TIMP2 G-418C (GG vs. GC vs. CC).
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f1-medscimonit-17-10-cr598: Expression of mRNA in peripheral blood lysates of sarcoid patients with various MMPs/TIMP2 polymorphisms. Horizontal lines show mean values: (A) MMP2 C-735T (CC vs. CT vs. TT); (B) MMP7 A-181G (AA vs. AG vs. GG); (C) MMP9 T-1702A (TT vs. AT and AA); (D) TIMP2 G-418C (GG vs. GC vs. CC).

Mentions: The distribution of alleles showed marginal deviation from the H-W equilibrium (p=0.06). There were no differences in genetic distribution between groups (Table 3). There were no differences in mRNA expression between genotypes in the study group (Figure 1A). Expression of proMMP2/MMP2 indicated by gel zymography did not show any differences between genotypes: proMMP2–4.07±0.33 vs. 3.79±0.17 vs. 3.82±0.38, and MMP2–4.48±0.34 vs. 4.27±0.21 vs. 4.35±0.49 103 units/ml BAL (for CC, CT and TT, respectively). CC genotype was more frequent in patients without LS (p=0.02). Patients with CC, CT and TT polymorphisms were not different in terms of parenchymal involvement (radiological stages), presence/absence of LS and LFT results.


The selected genetic polymorphisms of metalloproteinases MMP2, 7, 9 and MMP inhibitor TIMP2 in sarcoidosis.

Piotrowski WJ, Górski P, Pietras T, Fendler W, Szemraj J - Med. Sci. Monit. (2011)

Expression of mRNA in peripheral blood lysates of sarcoid patients with various MMPs/TIMP2 polymorphisms. Horizontal lines show mean values: (A) MMP2 C-735T (CC vs. CT vs. TT); (B) MMP7 A-181G (AA vs. AG vs. GG); (C) MMP9 T-1702A (TT vs. AT and AA); (D) TIMP2 G-418C (GG vs. GC vs. CC).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539463&req=5

f1-medscimonit-17-10-cr598: Expression of mRNA in peripheral blood lysates of sarcoid patients with various MMPs/TIMP2 polymorphisms. Horizontal lines show mean values: (A) MMP2 C-735T (CC vs. CT vs. TT); (B) MMP7 A-181G (AA vs. AG vs. GG); (C) MMP9 T-1702A (TT vs. AT and AA); (D) TIMP2 G-418C (GG vs. GC vs. CC).
Mentions: The distribution of alleles showed marginal deviation from the H-W equilibrium (p=0.06). There were no differences in genetic distribution between groups (Table 3). There were no differences in mRNA expression between genotypes in the study group (Figure 1A). Expression of proMMP2/MMP2 indicated by gel zymography did not show any differences between genotypes: proMMP2–4.07±0.33 vs. 3.79±0.17 vs. 3.82±0.38, and MMP2–4.48±0.34 vs. 4.27±0.21 vs. 4.35±0.49 103 units/ml BAL (for CC, CT and TT, respectively). CC genotype was more frequent in patients without LS (p=0.02). Patients with CC, CT and TT polymorphisms were not different in terms of parenchymal involvement (radiological stages), presence/absence of LS and LFT results.

Bottom Line: MMPs and TIMP2 mRNA were measured in peripheral blood lysate using real-time RT-PCR.DNA for genetic polymorphism was extracted from peripheral blood by GTC method.No differences were found between TT and AT/AA patients in terms of radiological stage, lung function test parameters, activity markers and the presence/absence of Löfgren syndrome.

View Article: PubMed Central - PubMed

Affiliation: Division of Pneumology and Allergy, Medical University of Lodz, Lodz, Poland.

ABSTRACT

Background: Increased activity of metalloproteinases may play a role in the initiation and propagation of inflammation in sarcoidosis, and may also be one of the factors responsible for the development of lung fibrosis. The aim of this study was to verify whether polymorphisms of MMP2 C-735T, MMP7 A-181G, MMP9 T-1702A and tissue inhibitor of metalloproteinase (TIMP)2 G-418C predispose to sarcoidosis.

Material/methods: The study included 139 patients with sarcoidosis and 100 healthy subjects. MMPs and TIMP2 mRNA were measured in peripheral blood lysate using real-time RT-PCR. DNA for genetic polymorphism was extracted from peripheral blood by GTC method. Protein concentrations in peripheral blood lysates were measured by ELISA, and MMP2 and 9 activities in BAL fluid were estimated by gel zymography.

Results: TT genotype in MMP9 T-1702A was more frequent in sarcoidosis (p<0.0001, OR = 13.71, 95% CI 7.02-26.80) and resulted in higher expression of MMP9 mRNA (p<0.0001). No differences were found between TT and AT/AA patients in terms of radiological stage, lung function test parameters, activity markers and the presence/absence of Löfgren syndrome. There were no differences in the distribution of MMP2, MMP7 and TIMP2 polymorphisms. Messenger RNAs, as well as protein concentrations of MMP2, 7, 9, and TIMP2 were elevated in patients with sarcoidosis (p<0.0001 for each).

Conclusions: The TT homozygotes of MMP9 T-1702A genotype may be predisposed to sarcoidosis. Elevated MMP2, 7, 9, and TIMP2 mRNAs suggest their inducibility.

Show MeSH
Related in: MedlinePlus