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
18489027
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
2008 Jun
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
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
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