Leukotriene B4 receptor locus gene characterisation and association studies in asthma

Tulah, Asif S. and Beghé, Bianca and Barton, Sheila J. and Holloway, John W. and Sayers, Ian (2012) Leukotriene B4 receptor locus gene characterisation and association studies in asthma. BMC Medical Genetics, 13 (Novemb). 11/1-11/11. ISSN 1471-2350

[img] PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Available under Licence Creative Commons Attribution.
Download (718kB)

Abstract

Background: Polymorphisms spanning genes involved in the production of leukotriene B4 (LTB4) e.g. ALOX5AP and

LTA4H are associated with asthma susceptibility, suggesting a role for LTB4 in disease. The contribution of LTB4

receptor polymorphism is currently unknown. The aim of this study was to characterise the genes for the two

pivotal LTB4 receptors, LTB4R1 and LTB4R2 in lung tissue and determine if polymorphisms spanning these genes are

associated with asthma and disease severity.

Methods: Rapid amplification of cDNA ends (RACE) was used to characterise the LTB4R1 and LTB4R2 gene structure

in lung. The LTB4R1/2 locus on chromosome 14q11.2 was screened for polymorphic variation. Six LTB4R single

nucleotide polymorphisms (SNPs) were genotyped in 370 Caucasian asthma families and 299 Adult Asthma

Individuals (n=1877 total) and were evaluated for association with asthma and severity (BTS) outcome measures

using Family Based Association Test, linear regression and chi square.

Results: LTB4R1 has complex mRNA arrangement including multiple 50

-untranslated exons, suggesting additional

levels of regulation. Three potential promoter regions across the LTB4R1/2 locus were identified with some airway

cell specificity. 22 SNPs (MAF>0.01) were validated across the LTB4R locus in the Caucasian population. LTB4R1 and

LTB4R2 SNPs were not associated with asthma susceptibility, FEV1 or severity.

Conclusions: LTB4R1 and LTB4R2 shows splice variation in the 50

-untranslated region and multiple promoter

regions. The functional significance of this is yet to be determined. Both receptor genes were shown to be

polymorphic. LTB4R polymorphisms do not appear to be susceptibility markers for the development of asthma in

Caucasian subjects

Item Type: Article
Keywords: Association, Asthma, Family based association test, Leukotriene, Leukotriene B4 receptor, Severity
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Medicine
Depositing User: Snowden, Ms Diane
Date Deposited: 08 Apr 2014 09:15
Last Modified: 15 Sep 2016 22:21
URI: http://eprints.nottingham.ac.uk/id/eprint/2625

Actions (Archive Staff Only)

Edit View Edit View