|
|
| PMID |
|
|
| TITLE |
|
| Characterization of two polymorphisms in the leukotriene C4 synthase gene in an Australian population of subjects with mild, moderate, and severe asthma. |
|
| ABSTRACT |
|
| BACKGROUND |
NlmCategory: BACKGROUND |
| The cysteinyl-leukotrienes (cys-LTs) are proinflammatory mediators that are important in the pathophysiology of asthma. LTC(4) synthase is a key enzyme in the cys-LT biosynthetic pathway, and studies in small populations have suggested that a promoter polymorphism (A(-444)C) in the gene might be associated with asthma severity and aspirin intolerance. |
| OBJECTIVE |
NlmCategory: OBJECTIVE |
| We sought to screen the LTC(4) synthase gene for polymorphisms and to determine whether there is an association between these polymorphisms and asthma severity or aspirin sensitivity in a large, well-phenotyped population and to determine whether this polymorphism is functionally relevant. |
| METHODS |
NlmCategory: METHODS |
| The coding regions of the LTC(4) synthase gene were screened for polymorphisms and the A(-444)C polymorphism was analyzed in a large Australian white adult population of mild (n=282), moderate (n=236), and severe asthmatic subjects (n=86) and nonasthmatic subjects (n=458), as well as in aspirin-intolerant asthmatic subjects (n=67). The functional activity of the promoter polymorphism was investigated by transient transfection of HL-60 cells with a promoter construct. |
| RESULTS |
NlmCategory: RESULTS |
| A new polymorphism was identified in intron 1 of the gene (IVS1-10c>a) but was not associated with asthma. Association studies showed that the A(-444)C polymorphism was weakly associated with asthma per se, but there was no association between the C(-444) allele and chronic asthma severity or aspirin intolerance. A meta-analysis of all the genetic studies conducted to date found significant between-study heterogeneity in C(-444) allele frequencies within different clinical subgroups. In vitro functional studies showed no significant differences in transcription efficiency between constructs containing the A(-444) allele or the C(-444) allele. |
| CONCLUSIONS |
NlmCategory: CONCLUSIONS |
| Our data confirm that, independent of transcriptional activity, the C(-444) allele in the LTC(4) synthase gene is weakly associated with the asthma phenotype, but it is not related to disease severity or aspirin intolerance. |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| pubmed |
2004/05/08 05:00 |
| medline |
2004/06/18 05:00 |
| entrez |
2004/05/08 05:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Kedda MA |
|
Kedda |
Mary-Anne |
MA |
|
Co-operative Research Centre for Asthma and the Asthma and Allergy Research Institute (Inc), Sir Charles Gairdner Hospital, University of Western Australia, Perth, WA 6009, Australia. |
| Shi J |
|
Shi |
Jing |
J |
|
|
| Duffy D |
|
Duffy |
David |
D |
|
|
| Phelps S |
|
Phelps |
Stephanie |
S |
|
|
| Yang I |
|
Yang |
Ian |
I |
|
|
| O'Hara K |
|
O'Hara |
Kirrily |
K |
|
|
| Fong K |
|
Fong |
Kwun |
K |
|
|
| Thompson PJ |
|
Thompson |
Philip J |
PJ |
|
|
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 113 |
| ISSUE: 5 |
| TITLE: The Journal of allergy and clinical immunology |
| ISOABBREVIATION: J. Allergy Clin. Immunol. |
| YEAR: 2004 |
| MONTH: May |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Print |
| ISSN: 0091-6749 |
| ISSNTYPE: Print |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: J Allergy Clin Immunol |
| COUNTRY: United States |
| ISSNLINKING: 0091-6749 |
| NLMUNIQUEID: 1275002 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| CommentIn |
J Allergy Clin Immunol. 2005 Jan;115(1):205 |
15637573 |
|
| CommentIn |
J Allergy Clin Immunol. 2005 Jan;115(1):206-7 |
15637574 |
|
|
| GRANTS |
|
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adolescent |
|
| Adult |
|
| Aged |
|
| Aged, 80 and over |
|
| Alleles |
|
| Aspirin |
|
| Asthma |
genetics |
| Australia |
genetics |
| Case-Control Studies |
genetics |
| Drug Tolerance |
genetics |
| Female |
genetics |
| Glutathione Transferase |
metabolism |
| HL-60 Cells |
metabolism |
| Humans |
metabolism |
| In Vitro Techniques |
metabolism |
| Male |
metabolism |
| Middle Aged |
metabolism |
| Phenotype |
metabolism |
| Polymorphism, Genetic |
metabolism |
| Polymorphism, Restriction Fragment Length |
metabolism |
| Polymorphism, Single-Stranded Conformational |
metabolism |
| Recombinant Proteins |
metabolism |
| Transfection |
metabolism |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
Recombinant Proteins |
| EC 2.5.1.18 |
Glutathione Transferase |
| EC 4.4.1.20 |
leukotriene-C4 synthase |
| R16CO5Y76E |
Aspirin |
|
| OTHER ID's |
|
|
|
