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Leukotriene B4 receptor locus gene characterisation and association studies in asthma

Leukotriene B4 receptor locus gene characterisation and association studies in asthma
Leukotriene B4 receptor locus gene characterisation and association studies in asthma
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 5[prime]-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 5[prime]-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.
association, asthma, family based association test, leukotriene, leukotriene B4 receptor, RACE, severity
1471-2350
110
Tulah, Asif S.
33c5205a-8c51-47c1-920a-445f04f23697
Beghé, Bianca
950a3274-9729-4352-9309-edb772f7d278
Barton, Sheila J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Sayers, Ian
8595fc2e-102b-406c-ba26-269b8bdba786
Tulah, Asif S.
33c5205a-8c51-47c1-920a-445f04f23697
Beghé, Bianca
950a3274-9729-4352-9309-edb772f7d278
Barton, Sheila J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Sayers, Ian
8595fc2e-102b-406c-ba26-269b8bdba786

Tulah, Asif S., Beghé, Bianca, Barton, Sheila J., Holloway, John W. and Sayers, Ian (2012) Leukotriene B4 receptor locus gene characterisation and association studies in asthma. BMC Medical Genetics, 13 (1), 110. (doi:10.1186/1471-2350-13-110). (PMID:23167751)

Record type: Article

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 5[prime]-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 5[prime]-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.

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More information

e-pub ahead of print date: 20 November 2012
Keywords: association, asthma, family based association test, leukotriene, leukotriene B4 receptor, RACE, severity
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 345531
URI: http://eprints.soton.ac.uk/id/eprint/345531
ISSN: 1471-2350
PURE UUID: 949a6e55-a50f-4f97-ad7f-9f352afd947e
ORCID for Sheila J. Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 23 Nov 2012 10:13
Last modified: 15 Mar 2024 03:10

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Contributors

Author: Asif S. Tulah
Author: Bianca Beghé
Author: Ian Sayers

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