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5-Lipoxygenase pathway gene polymorphisms and asthma severity in UK families

Lookup NU author(s): Dr Asif Tulah


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Rationale: Leukotrienes are lipid mediators important in inflammatory disorders such as asthma. It has previously been shown that polymorphisms spanning genes involved in the production and activity of cysteinyl leukotrienes (CysLTs) and the production of leukotriene B4 (LTB4) (specifically LTA4H) are associated with asthma susceptibility. In the present study we aimed to investigate whether these SNPs contribute to the severity of asthma defined by British Thoracic Society (BTS) Step or by nocturnal symptoms. We also extend these analyses by including polymorphisms spanning the LTB4 receptor locus (LTB4R). Methods: 26 SNPs were genotyped across ALOX5 (1), ALOX5AP (10), LTC4S (2), LTA4H (5), CYSLTR1 (1), LTB4R (6) and MRP1 (1) in 341 UK families from Southampton with at least two biological siblings with physician diagnosed asthma. Association with BTS step 1 to 5 or nocturnal asthma symptoms (Y/N) was determined by FBAT (Family-Based Association Test) using the additive model. Results: No SNP association survived correction for multiple testing, however there was suggestive evidence for associations for 6/26 SNPs (p<0.038-0.001) and BTS defined severity. These polymorphisms were within ALOX5AP (2), LTA4H (3) and MRP1 (1). The ALOX5AP SG13S41G (intron 4) SNP that was associated with BTS defined severity (p=0.001) was also associated with nocturnal symptoms (p=0.03). Conclusions: These data provide tentative support for a role of SNPs spanning LT synthesising and transport genes influencing asthma severity.

Publication metadata

Author(s): Tulah AS, Holloway JW, Sayers I

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: The American Thoracic Society International Conference

Year of Conference: 2013

Pages: A2709

ISSN: 1535-4970

Publisher: American Thoracic Society


DOI: 10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A2709

Series Title: American Journal of Respiratory and Critical Care Medicine