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PMID |
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TITLE |
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Cyclooxygenase-2 gene polymorphisms in an Australian population: association of the -1195G > A promoter polymorphism with mild asthma. |
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ABSTRACT |
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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. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
aheadofprint |
2008/04/11 |
pubmed |
2008/05/21 09:00 |
medline |
2008/07/29 09:00 |
entrez |
2008/05/21 09:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Shi J |
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Shi |
J |
J |
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Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, The University of Western Australia, Perth, WA, Australia. |
Misso NL |
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Misso |
N L |
NL |
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Kedda MA |
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Kedda |
M-A |
MA |
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Horn J |
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Horn |
J |
J |
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Welch MD |
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Welch |
M D |
MD |
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Duffy DL |
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Duffy |
D L |
DL |
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Williams C |
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Williams |
C |
C |
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Thompson PJ |
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Thompson |
P J |
PJ |
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INVESTIGATORS |
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JOURNAL |
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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 |
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MEDLINE JOURNAL |
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MEDLINETA: Clin Exp Allergy |
COUNTRY: England |
ISSNLINKING: 0954-7894 |
NLMUNIQUEID: 8906443 |
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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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GRANTS |
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GENERAL NOTE |
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KEYWORDS |
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MESH HEADINGS |
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DESCRIPTORNAME |
QUALIFIERNAME |
Adult |
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Aged |
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Aged, 80 and over |
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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 |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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REGISTRYNUMBER |
NAMEOFSUBSTANCE |
EC 1.14.99.1 |
Cyclooxygenase 2 |
R16CO5Y76E |
Aspirin |
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OTHER ID's |
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