Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
16061701
TITLE
A novel tissue inhibitor of metalloproteinase-1 (TIMP-1) polymorphism associated with asthma in Australian women.
ABSTRACT
BACKGROUND NlmCategory: 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 NlmCategory: 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 NlmCategory: RESULTS
MMP-9 -1562C>T and 836G>A (Arg279Gln) were not associated with asthma (p> or =0.15) or asthma severity (p> or =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 -861C>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% CI 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 NlmCategory: 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.
DATE PUBLISHED
2005 Aug
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2005/08/03 09:00
medline 2005/09/13 09:00
entrez 2005/08/03 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Lose F Lose F F Asthma and Allergy Research Institute, QEII Medical Centre, Nedlands, WA 6009, Australia.
Thompson PJ Thompson P J PJ
Duffy D Duffy D D
Stewart GA Stewart G A GA
Kedda MA Kedda M-A MA
INVESTIGATORS
JOURNAL
VOLUME: 60
ISSUE: 8
TITLE: Thorax
ISOABBREVIATION: Thorax
YEAR: 2005
MONTH: Aug
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0040-6376
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Thorax
COUNTRY: England
ISSNLINKING: 0040-6376
NLMUNIQUEID: 0417353
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Aged
Aged, 80 and over
Asthma physiopathology
Australia physiopathology
Female physiopathology
Forced Expiratory Volume physiology
Haplotypes physiology
Humans physiology
Matrix Metalloproteinase 9 genetics
Middle Aged genetics
Polymorphism, Genetic genetics
Tissue Inhibitor of Metalloproteinase-1 genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Tissue Inhibitor of Metalloproteinase-1
EC 3.4.24.35 Matrix Metalloproteinase 9
OTHER ID's
OTHERID SOURCE
PMC1747496 NLM