A novel tissue inhibitor of metalloproteinase-1 (TIMP-1) polymorphism associated with asthma in Australian women

Felicity Lose; P J Thompson; D Duffy; G A Stewart; M A Kedda

doi:10.1136/thx.2004.026930

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A novel tissue inhibitor of metalloproteinase-1 (TIMP-1) polymorphism associated with asthma in Australian women

Journal article

Peer reviewed

A novel tissue inhibitor of metalloproteinase-1 (TIMP-1) polymorphism associated with asthma in Australian women

Felicity Lose, P J Thompson, D Duffy, G A Stewart and M A Kedda

Thorax, Vol.60(8), pp.623-628

2005

DOI: https://doi.org/10.1136/thx.2004.026930

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Abstract

Background: Airway remodelling is a characteristic feature of chronic asthma and there is evidence that an airway imbalance between levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) is associated with airway remodelling. On this basis, we hypothesised that polymorphisms in the MMP-9 and TIMP-1 genes were associated with the disease process. Methods: A number of MMP-9 and TIMP-1 gene polymorphisms were examined in an adult white Australian population of mild (n = 259), moderate (n = 213) and severe (n = 71) asthmatics and non-asthmatic controls (n = 406) using PCR-RFLP and PCR-SSCP analyses. Results: MMP-9 - 1562C>T and 836G>A (Arg279Gln) were not associated with asthma (p≥0.15) or asthma severity (p≥0.13), and TIMP-1 434T>C (Phe124Phe) was not associated with asthma in women (p = 0.094) or men (p = 0.207). In this population, MMP-9 -861 C>T and TIMP-1 323C>T (Pro87Pro) were not informative (with minor allele frequencies of <1%), and MMP-9 -1702T>A and TIMP-1 595C>T (Ser178Phe) were not detectable. However, a novel polymorphism was detected in the TIMP-1 gene 536C>T (Ile158Ile) which was significantly associated with asthma in women (p = 0.011; OR = 5.54, 95% Cl 1.66 to 34.4) but not in men (p = 1.0). 536C>T was found to be in linkage disequilibrium with 434T>C, and haplotype analysis supported an association with asthma (p = 0.014). Conclusions: This is the first reported association between a polymorphism in the TIMP-1 gene and asthma, and supports the hypothesis that the protease/antiprotease balance has an important role in this common disease.

Details

Title: A novel tissue inhibitor of metalloproteinase-1 (TIMP-1) polymorphism associated with asthma in Australian women
Authors: Felicity Lose (Author) - University of Western Australia
P J Thompson (Author) - University of Western Australia
D Duffy (Author) - Queensland Institute of Medical Research
G A Stewart (Author) - University of Western Australia
M A Kedda (Author) - University of Western Australia
Publication details: Thorax, Vol.60(8), pp.623-628
Publisher: B M J Group
Date published: 2005
DOI: 10.1136/thx.2004.026930
ISSN: 0040-6376
Organisation Unit: University of the Sunshine Coast, Queensland; Office of Research
Language: English
Record Identifier: 99451179602621
Output Type: Journal article

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Collaboration types: Domestic collaboration
Web Of Science research areas: Respiratory System

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