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Determination of structure and transcriptional regulation of CYSLTR1 and an association study with asthma and rhinitis

Determination of structure and transcriptional regulation of CYSLTR1 and an association study... Pharmacologic studies have revealed that cysteinyl leukotrienes (CYSLTs) act through two receptors, cysteinyl leukotriene receptor 1 (CYSLTR1) and CYSLTR2. CYSLTR1 antagonists are widely used to treat asthma and rhinitis. In this study, we characterized the genomic structure and transcriptional regulation of CYSLTR1 and examined associations between CYSLTR1 polymorphisms and asthma/rhinitis. The experiment of rapid amplification of cDNA end revealed that CYSLTR1 contains three exons and that the entire open reading frame is located in exon 3. Reverse transcriptase‐polymerase chain reaction showed that there were multiple splice variants of CYSLTR1 and that the transcript expression patterns differed from tissues and cell types. The promoter region of CYSLTR1 is from −665 to −30 bp relative to the transcription start site. We identified four polymorphisms (c.‐618‐434T/C, c.‐618‐275C/A, c.‐618‐136G/A, and 927C/T), and transmission disequilibrium tests revealed that none of these polymorphisms was associated with the development of asthma/rhinitis. However, the TCG and CAA haplotypes in the promoter region caused different transcriptional activity. Our findings indicate that CYSLTR1 polymorphisms are not likely to be involved in the development of asthma/rhinitis, but it is possible that these polymorphisms could influence drug responses in individuals with atopic diseases. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Pediatric Allergy and Immunology Wiley

Determination of structure and transcriptional regulation of CYSLTR1 and an association study with asthma and rhinitis

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References (30)

Publisher
Wiley
Copyright
Copyright © 2006 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0905-6157
eISSN
1399-3038
DOI
10.1111/j.1399-3038.2005.00347.x
pmid
16771777
Publisher site
See Article on Publisher Site

Abstract

Pharmacologic studies have revealed that cysteinyl leukotrienes (CYSLTs) act through two receptors, cysteinyl leukotriene receptor 1 (CYSLTR1) and CYSLTR2. CYSLTR1 antagonists are widely used to treat asthma and rhinitis. In this study, we characterized the genomic structure and transcriptional regulation of CYSLTR1 and examined associations between CYSLTR1 polymorphisms and asthma/rhinitis. The experiment of rapid amplification of cDNA end revealed that CYSLTR1 contains three exons and that the entire open reading frame is located in exon 3. Reverse transcriptase‐polymerase chain reaction showed that there were multiple splice variants of CYSLTR1 and that the transcript expression patterns differed from tissues and cell types. The promoter region of CYSLTR1 is from −665 to −30 bp relative to the transcription start site. We identified four polymorphisms (c.‐618‐434T/C, c.‐618‐275C/A, c.‐618‐136G/A, and 927C/T), and transmission disequilibrium tests revealed that none of these polymorphisms was associated with the development of asthma/rhinitis. However, the TCG and CAA haplotypes in the promoter region caused different transcriptional activity. Our findings indicate that CYSLTR1 polymorphisms are not likely to be involved in the development of asthma/rhinitis, but it is possible that these polymorphisms could influence drug responses in individuals with atopic diseases.

Journal

Pediatric Allergy and Immunology – Wiley

Published: Jun 1, 2006

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