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|
| PMID |
|
|
| TITLE |
|
| Cyclooxygenase-2 gene polymorphisms in an Australian population: association of the -1195G > A promoter polymorphism with mild asthma. |
|
| ABSTRACT |
|
| BACKGROUND |
NlmCategory: BACKGROUND |
| Cyclooxygenase (COX)-2 is an inducible enzyme responsible for catalysing the formation of prostaglandins (PGs) in settings of inflammation. Single nucleotide polymorphisms (SNPs) of the COX-2 gene may influence gene transcription and PG production in the asthmatic airway. |
| OBJECTIVE |
NlmCategory: OBJECTIVE |
| To evaluate the frequencies of COX-2 SNPs in an Australian Caucasian population, and determine potential associations between common COX-2 promoter SNPs and asthma, asthma severity and aspirin-intolerant asthma (AIA). |
| METHODS |
NlmCategory: METHODS |
| The frequencies of 25 COX-2 SNPs were determined in a random population (n=176). The SNPs with a minor allele frequency of >10% were then studied in asthmatic (n=663), non-asthmatic controls (n=513) and AIA subjects (n=58). Genotype, allele and haplotype associations were assessed. Functional assessment of SNPs was performed by transfection into HeLa cells measured using the luciferase dual-reporter assay system. |
| RESULTS |
NlmCategory: RESULTS |
| Eighteen COX-2 SNPs were not detected, five were rare and two promoter SNPs, -1195G>A (rs689465), and -1290A>G (rs689466), were further studied. The A allele of the -1195 SNP was present at a significantly higher frequency among all asthmatic subjects (P=0.012). Over 60% of the asthmatic individuals were -1195A homozygotes compared with 54.6% of the control subjects (odds ratio, 1.35; 95% CI, 1.06-1.72, P=0.03). After classifying for severity, the mild asthmatics represented 64.6% of -1195AA individuals, the highest of all the asthma groups compared with 54.6% of the control subjects (odds ratio, 1.5; 95% CI, 1.12-2.02, P=0.02). The -1290A/-1195G/-765G haplotype was associated with a reduced incidence of asthma (odds ratio, 0.76; 95% CI, 0.61-0.95, P=0.017). |
| CONCLUSION |
NlmCategory: CONCLUSIONS |
| The -1195G>A polymorphism appears to be associated with asthma, and in particular with mild asthma. |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| aheadofprint |
2008/04/11 |
| pubmed |
2008/05/21 09:00 |
| medline |
2008/07/29 09:00 |
| entrez |
2008/05/21 09:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Shi J |
|
Shi |
J |
J |
|
Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, The University of Western Australia, Perth, WA, Australia. |
| Misso NL |
|
Misso |
N L |
NL |
|
|
| Kedda MA |
|
Kedda |
M-A |
MA |
|
|
| Horn J |
|
Horn |
J |
J |
|
|
| Welch MD |
|
Welch |
M D |
MD |
|
|
| Duffy DL |
|
Duffy |
D L |
DL |
|
|
| Williams C |
|
Williams |
C |
C |
|
|
| Thompson PJ |
|
Thompson |
P J |
PJ |
|
|
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 38 |
| ISSUE: 6 |
| TITLE: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology |
| ISOABBREVIATION: Clin. Exp. Allergy |
| YEAR: 2008 |
| MONTH: Jun |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1365-2222 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Clin Exp Allergy |
| COUNTRY: England |
| ISSNLINKING: 0954-7894 |
| NLMUNIQUEID: 8906443 |
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| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, Non-U.S. Gov't |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
|
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| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adult |
|
| Aged |
|
| Aged, 80 and over |
|
| Aspirin |
adverse effects |
| Asthma |
genetics |
| Australia |
genetics |
| Case-Control Studies |
genetics |
| Cyclooxygenase 2 |
genetics |
| European Continental Ancestry Group |
genetics |
| Female |
genetics |
| Gene Frequency |
genetics |
| Genetic Predisposition to Disease |
genetics |
| Haplotypes |
genetics |
| HeLa Cells |
genetics |
| Humans |
genetics |
| Male |
genetics |
| Middle Aged |
genetics |
| Phenotype |
genetics |
| Plasmids |
genetics |
| Polymerase Chain Reaction |
genetics |
| Polymorphism, Single Nucleotide |
genetics |
| Promoter Regions, Genetic |
genetics |
| Sequence Analysis, DNA |
genetics |
| Transfection |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| EC 1.14.99.1 |
Cyclooxygenase 2 |
| R16CO5Y76E |
Aspirin |
|
| OTHER ID's |
|
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|
