|
|
| PMID |
|
|
| 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 |
|
|
| 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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| CommentIn |
Thorax. 2005 Aug;60(8):617-8 |
16061698 |
|
|
| 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 |
|
|
