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PMID |
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TITLE |
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A novel tissue inhibitor of metalloproteinase-1 (TIMP-1) polymorphism associated with asthma in Australian women. |
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ABSTRACT |
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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. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
pubmed |
2005/08/03 09:00 |
medline |
2005/09/13 09:00 |
entrez |
2005/08/03 09:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Lose F |
|
Lose |
F |
F |
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Asthma and Allergy Research Institute, QEII Medical Centre, Nedlands, WA 6009, Australia. |
Thompson PJ |
|
Thompson |
P J |
PJ |
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Duffy D |
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Duffy |
D |
D |
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Stewart GA |
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Stewart |
G A |
GA |
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Kedda MA |
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Kedda |
M-A |
MA |
|
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INVESTIGATORS |
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JOURNAL |
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VOLUME: 60 |
ISSUE: 8 |
TITLE: Thorax |
ISOABBREVIATION: Thorax |
YEAR: 2005 |
MONTH: Aug |
DAY: |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Print |
ISSN: 0040-6376 |
ISSNTYPE: Print |
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MEDLINE JOURNAL |
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MEDLINETA: Thorax |
COUNTRY: England |
ISSNLINKING: 0040-6376 |
NLMUNIQUEID: 0417353 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
Research Support, Non-U.S. Gov't |
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COMMENTS AND CORRECTIONS |
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REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
Cites |
Hum Genet. 1999 Nov;105(5):418-23 |
10598806 |
|
Cites |
J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):530-3 |
10482823 |
|
Cites |
Trends Biochem Sci. 2000 Mar;25(3):106-10 |
10694877 |
|
Cites |
Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):1157-61 |
10988146 |
|
Cites |
Allergy. 2000 Sep;55(9):900-1 |
11003463 |
|
Cites |
Arterioscler Thromb Vasc Biol. 2001 Sep;21(9):1446-50 |
11557670 |
|
Cites |
Biochem Biophys Res Commun. 2001 Nov 23;289(1):116-9 |
11708786 |
|
Cites |
Clin Exp Allergy. 2002 Feb;32(2):217-23 |
11929485 |
|
Cites |
Nat Rev Genet. 2002 Apr;3(4):285-98 |
11967553 |
|
Cites |
Am J Pathol. 2002 Aug;161(2):491-8 |
12163374 |
|
Cites |
Chest. 2002 Nov;122(5):1543-52 |
12426251 |
|
Cites |
Chest. 2002 Nov;122(5):1553-9 |
12426252 |
|
Cites |
J Allergy Clin Immunol. 2003 Jun;111(6):1345-52 |
12789238 |
|
Cites |
Nucleic Acids Res. 2003 Jul 1;31(13):3568-71 |
12824367 |
|
Cites |
Genet Epidemiol. 2003 Sep;25(2):115-21 |
12916020 |
|
Cites |
Thorax. 2003 Sep;58(9):757-60 |
12947131 |
|
Cites |
Hum Mutat. 2003 Nov;22(5):418 |
14517959 |
|
Cites |
Hum Genet. 2003 Nov;113(6):551-4 |
13680360 |
|
Cites |
J Allergy Clin Immunol. 2004 May;113(5):889-95 |
15131571 |
|
Cites |
J Biol Chem. 1989 Jan 25;264(3):1353-6 |
2536363 |
|
Cites |
Hum Genet. 1992 Sep-Oct;90(1-2):41-54 |
1427786 |
|
Cites |
Methods Enzymol. 1995;248:496-510 |
7674941 |
|
Cites |
J Allergy Clin Immunol. 1998 Nov;102(5):783-8 |
9819295 |
|
Cites |
Am J Respir Crit Care Med. 1998 Dec;158(6):1945-50 |
9847290 |
|
Cites |
Circulation. 1999 Apr 13;99(14):1788-94 |
10199873 |
|
Cites |
Matrix Biol. 1999 Apr;18(2):121-4 |
10372551 |
|
CommentIn |
Thorax. 2005 Aug;60(8):617-8 |
16061698 |
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GRANTS |
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GENERAL NOTE |
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KEYWORDS |
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MESH HEADINGS |
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DESCRIPTORNAME |
QUALIFIERNAME |
Adolescent |
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Adult |
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Aged |
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Aged, 80 and over |
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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 |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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REGISTRYNUMBER |
NAMEOFSUBSTANCE |
0 |
Tissue Inhibitor of Metalloproteinase-1 |
EC 3.4.24.35 |
Matrix Metalloproteinase 9 |
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OTHER ID's |
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OTHERID |
SOURCE |
PMC1747496 |
NLM |
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