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.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
15784112
TITLE
Polymorphisms in the 5-lipoxygenase activating protein (ALOX5AP) gene are not associated with asthma in an Australian population.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
The cysteinyl-leukotrienes (cys-LTs) are important pro-inflammatory mediators in asthma, and have been shown to have a role in specific disease subtypes, including asthma severity. Few studies have investigated the role of polymorphisms in the ALOX5AP gene, encoding 5-lipoxygenase activating protein (FLAP), and asthma. We hypothesized that polymorphisms in this gene are associated with asthma and in particular, with asthma severity, in an Australian population.
OBJECTIVE NlmCategory: OBJECTIVE
To screen the coding region of the ALOX5AP gene for polymorphisms and to determine the association between previously described polymorphisms and asthma and asthma severity in an Australian population.
METHODS NlmCategory: METHODS
We used PCR-SSCP and PCR-RFLP analysis to examine a previously described promoter polyA variable repeat polymorphism and two intronic polymorphisms (IVS2+12C>A, IVS2+105T>C), and to screen all five exons of the gene for new polymorphisms, in a large Australian population of randomly selected, non-asthmatic controls (n=457), mild asthmatics (n=274), moderate asthmatics (n=231) and severe asthmatics (n=79).
RESULTS NlmCategory: RESULTS
We confirmed the presence of two polymorphisms in intron 2 and found no association between these polymorphisms and asthma or asthma severity, nor between a promoter polymorphism in the ALOX5AP gene and asthma or asthma severity. Gene fragment analysis of the promoter polymorphism revealed novel, conserved repeat numbers in our population, and no new polymorphisms were found in the coding region of the gene.
CONCLUSION NlmCategory: CONCLUSIONS
These findings in a large, well characterized asthma population, reveal that, while FLAP is an important enzyme in cys-LTs biosynthesis, polymorphisms in the ALOX5AP gene are not likely to be functionally associated with the asthma phenotype.
DATE PUBLISHED
2005 Mar
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2005/03/24 09:00
medline 2005/09/01 09:00
entrez 2005/03/24 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Kedda MA Kedda M-A MA The Co-operative Research Centre for Asthma, the Asthma and Allergy Research Institute (Inc.), Perth, Australia.
Worsley P Worsley P P
Shi J Shi J J
Phelps S Phelps S S
Duffy D Duffy D D
Thompson PJ Thompson P J PJ
INVESTIGATORS
JOURNAL
VOLUME: 35
ISSUE: 3
TITLE: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
ISOABBREVIATION: Clin. Exp. Allergy
YEAR: 2005
MONTH: Mar
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0954-7894
ISSNTYPE: Print
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
5-Lipoxygenase-Activating Proteins
Adult
Aged
Asthma genetics
Australia genetics
Carrier Proteins genetics
Case-Control Studies genetics
European Continental Ancestry Group genetics
Exons genetics
Female genetics
Humans genetics
Introns genetics
Male genetics
Membrane Proteins genetics
Middle Aged genetics
Polymorphism, Genetic genetics
Polymorphism, Restriction Fragment Length genetics
Polymorphism, Single-Stranded Conformational genetics
Promoter Regions, Genetic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 5-Lipoxygenase-Activating Proteins
0 ALOX5AP protein, human
0 Carrier Proteins
0 Membrane Proteins
OTHER ID's