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Matrix Metalloproteinases Gene Variants in Idiopathic Disseminated Bronchiectasis
  1. Marija Stankovic, MSc*,
  2. Aleksandra Nikolic, MSc*,
  3. Aleksandra Divac, PhD*,
  4. Ljiljana Rakicevic, MSc*,
  5. Andrija Tomovic, PhD,
  6. Marija Mitic-Milikic, MD, PhD,
  7. Ljudmila Nagorni-Obradovic, MD, PhD,
  8. Milan Grujic, MD,
  9. Natasa Petrovic-Stanojevic, MD, MSc§,
  10. Marina Andjelic-Jelic, MD, MSc§,
  11. Vesna Dopudja-Pantic, MD, MSc§,
  12. Dragica Radojkovic, PhD*
  1. From the *Institute of Molecular Genetics and Genetic Engineering, Belgrade, Serbia; †3V Biosciences, c/o Institute of Biochemistry, ETH Hoenggerberg HPM E17, Zurich, Switzerland; ‡Institute for Tuberculosis and Lung Disease, University Clinical Center of Serbia; and §Zvezdara University Medical Center, Belgrade, Serbia.
  1. Received August 28, 2008, and in revised form November 20, 2008.
  2. Accepted for publication December 9, 2008.
  3. This work was supported by grant 143051 from Ministry of Science and Technological Development of Republic of Serbia.
  4. Reprints: Marija Stankovic, Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, P.O.Box 23, 11010 Belgrade, Serbia. E-mail: marijast{at}imgge.bg.ac.rs.

Abstract

Background The excess of matrix metalloproteinases (MMPs) might be associated with the airways destruction or dilatation in bronchiectasis. The functional promoter polymorphisms of MMP1 and MMP9 genes, involved in the extracellular matrix remodeling, might increase the expression of MMPs leading to the development of bronchiectasis.

Methods Detection of MMP1 G-1607GG and MMP9 C-1562T gene variants was performed on 37 patients with idiopathic disseminated bronchiectasis and 102 control subjects. We also described a novel method for simple and rapid detection of MMP1 G-1607GG polymorphism.

Results The frequency of -1607GG allele was significantly higher in the group of patients than in control subjects (P = 0.014). The heterozygote genotype showed association with bronchiectasis (odds ratio, 5.3; 95% confidence intervals, 1.4-20.0). The association was even stronger in homozygotes for -1607GG allele (odds ration, 8.7; 95% confidence intervals, 1.9-41.0). The allelic and genotype frequencies of MMP9 C-1562T variant did not show significant differences between the groups.

Conclusions This is the first report concerning a role of MMP1 G-1607GG and MMP9 C-1562T variants in pathogenesis of idiopathic disseminated bronchiectasis. The results of our study revealed the association of -1607GG allele and the lack of association of MMP9 C-1562T variant with the disease.

Key Words
  • idiopathic disseminated bronchiectasis
  • promoter polymorphisms
  • MMP1
  • MMP9
  • association

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