TITLE

Promoter variants in tissue inhibitor of metalloproteinase-3 (TIMP-3) protect against susceptibility in pigeon breeders' disease

AUTHOR(S)
Hill, M. R.; Briggs, I.; Montaña, M. M.; Estrada, A.; Laurent, G. J.; Selman, M.; Pordo, A.
PUB. DATE
July 2004
SOURCE
Thorax;Jul2004, Vol. 59 Issue 7, p586
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Tissue inhibitors of metalloproteinases (TIMPs) play a major role in extracellular matrix turnover in the lung. However, in chronic lung disorders such as idiopathic pulmonary fibrosis (IPF) and pigeon breeders' disease (PBD), TIMPs may promote an adverse non-degradative environment. We hypothesised that polymorphisms in TIMP-3 could affect susceptibility to IPF and PBD. Methods: Two promoter variants, -915A>G and -1296T>C, were genotyped in 323 healthy subjects, 94 subjects with IPF, 115 with PBD, and 90 exposed to avian antigen but without PBD. The severity of fibrosis in lung tissue and the clinical outcome after 1 year was determined in the PBD group. Results: The variants did not influence susceptibility to IPF, but the rare alleles of both variants appeared to be protective against susceptibility to PBD (odds ratio (OR) for carriage of at least one rare allele from either variant 0.48, 95% CI 0.30 to 0.76, p=0.002). Haplotype analysis of positions -915 and -1296 estimated four haplotypes: *A*T *G*T *A*C and *G*C respectively. Their frequencies differed overall between subjects with PBD and healthy subjects (p = 0.0049) and this was attributable primarily to the *G*C haplotype (OR 0.53, 95% CI 0.36 to 0.77, p=0.001). The severity of fibrosis correlated with poorer outcome in the PBD group (r=0.73, p<0.01) but no relationship was seen between the *G*C hapiotype and outcome or fibrosis. However, PBD subjects with the *G*C haplotype did have proportionally fewer lymphocytes in their bronchoalveolar fluid than those with the common *A*T haplotype (p = 0.029). Conclusions: TIMP-3 variants appear to contribute to susceptibility to PBD. This may be through the inflammatory reaction rather than the fibrotic reaction.
ACCESSION #
13997059

 

Related Articles

  • Myeloperoxidase Promoter Polymorphism -463G Is Associated With More Severe Clinical Expression of Cystic Fibrosis Pulmonary Disease. Reynolds, Wanda F.; Sermet-Gaudelus, Isabelle; Gausson, Val�rie; Feuillet, Marie-No�lle; Bonnefont, Jean-Paul; Lenoir, G�rard; Descamps-Latscha, B�atrice; Witko-Sarsat, V�ronique // Mediators of Inflammation;4/1/2006, Vol. 2006 Issue 2, p1 

    The severity of cystic fibrosis (CF) pulmonary disease is not directly related to CFTR genotype but depends upon several parameters, including neutrophil-dominated inflammation. Identification of agents modulating inflammation constitutes a relevant goal. Myeloperoxidase (MPO) is involved in...

  • ADRA2A IS A CYSTIC FIBROSIS MODIFIER GENE. MARSON, F. A. L.; REZENDE, L. M.; FURGERI, D. T.; RIBEIRO, A. F.; RIBEIRO, J. D.; BERTUZZO, C. S. // International Journal of Genetics;2013, Vol. 5 Issue 1, p125 

    Background: Cystic fibrosis (CF) is an autosomal disease with characteristics of a complex disease. Understanding ADRA2A polymorphisms are important to elucidate clinical variability that is encountered in inflammatory diseases including CF, for which diabetes is an important comorbidity beyond...

  • AGER -429T/C Is Associated with an Increased Lung Disease Severity in Cystic Fibrosis. Beucher, Julie; Boëlle, Pierre-Yves; Busson, Pierre-François; Muselet-Charlier, Cé line; Clement, Annick; Corvol, Harriet // PLoS ONE;Jul2012, Vol. 7 Issue 7, p1 

    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients...

  • The ACE gene D/I polymorphism as a modulator of severity of cystic fibrosis. .Marson, Fernando A. L.; Bertuzzo, Carmen S.; Hortencio, Ta¡s D. R.; Ribeiro, Jos‚ D.; Bonadia, Luciana C.; Ribeiro, Ant“nio F. // BMC Pulmonary Medicine;2012, Vol. 12 Issue 1, p41 

    Background: Cystic Fibrosis (CF) is a monogenic disease with complex expression because of the action of genetic and environmental factors. We investigated whether the ACE gene D/I polymorphism is associated with severity of CF. Methods: A cross-sectional study was performed, from 2009 to 2011,...

  • The Chitinase-Like Protein YKL-40 Modulates Cystic Fibrosis Lung Disease. Hector, Andreas; Kormann, Michael S. D.; Mack, Ines; Latzin, Philipp; Casaulta, Carmen; Kieninger, Elisabeth; Zhe Zhou; Yildirim, Ali Ö.; Bohla, Alexander; Rieber, Nikolaus; Kappler, Matthias; Koller, Barbara; Eber, Ernst; Eickmeier, Olaf; Zielen, Stefan; Eickelberg, Oliver; Griese, Matthias; Mall, Marcus A.; Hartl, Dominik // PLoS ONE;2011, Vol. 6 Issue 9, p1 

    The chitinase-like protein YKL-40 was found to be increased in patients with severe asthma and chronic obstructive pulmonary disease (COPD), two disease conditions featuring neutrophilic infiltrates. Based on these studies and a previous report indicating that neutrophils secrete YKL-40, we...

  • Initial Treatment of Cystic Fibrosis. Roach, E. S.; Sinal, Sara H. // Clinical Pediatrics;Aug1989, Vol. 28 Issue 8, p371 

    Four infants with newly diagnosed cystic fibrosis developed a bulging anterior fontanel within days of starting enzyme replacement treatment. In the same time period, 41 hospitalized patients less than t year of age were diagnosed as having cystic fibrosis and treated, suggesting that increased...

  • Slc26a6 regulates CFTR activity in vivo to determine pancreatic duct HCO3− secretion: relevance to cystic fibrosis. Wang, Youxue; Soyombo, Abigail A.; Shcheynikov, Nikolay; Weizhong Zeng; Dorwart, Michael; Marino, Christopher R.; Thomas, Philip J.; Muallem, Shmuel // EMBO Journal;10/25/2006, Vol. 25 Issue 21, p5049 

    Fluid and HCO3− secretion are vital functions of the pancreatic duct and other secretory epithelia. CFTR and Cl−/HCO3− exchange activity at the luminal membrane are required for these functions. The molecular identity of the Cl−/HCO3− exchangers and their...

  • Free DNA in Cystic Fibrosis Airway Fluids Correlates with Airflow Obstruction. Marcos, Veronica; Zhou-Suckow, Zhe; Önder Yildirim, Ali; Bohla, Alexander; Hector, Andreas; Vitkov, Ljubomir; Krautgartner, Wolf Dietrich; Stoiber, Walter; Griese, Matthias; Eickelberg, Oliver; Mall, Marcus A.; Hartl, Dominik // Mediators of Inflammation;3/31/2015, Vol. 2015, p1 

    Chronic obstructive lung disease determines morbidity and mortality of patients with cystic fibrosis (CF). CF airways are characterized by a nonresolving neutrophilic inflammation. After pathogen contact or prolonged activation, neutrophils release DNA fibres decorated with antimicrobial...

  • Polymorphisms of the Cytochrome P450 (CYP1A1, CYP2E1) and Microsomal Epoxide Hydrolase (mEPHX) Genes in Cystic Fibrosis and Chronic Respiratory Disease. Korytina, G. F.; Yanbaeva, D. G.; Viktorova, T. V. // Molecular Biology;Sep/Oct2003, Vol. 37 Issue 5, p663 

    Frequencies of CYP1A1, CYP2E1, and mEPHX polymorphic variants were analyzed in cystic fibrosis, chronic obstructive lung disease, bronchiectatic disease, chronic nonobstructive bronchitis, and recurring bronchitis. Mutations in CYP1A1 and mEPHX were shown to modify the severity of respiratory...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics