Allelic association and functional studies of promoter polymorphism in the leukotriene C4 synthase gene (LTC4S) in asthma.

Sayers, I.; Barton, S.; Rorke, S.; Beghe', Bianca; Hayward, B.; Van Eerdewegh, P.; Keith, T.; Clough, J. B.; Ye, S.; Holloway, J. W.; Sampson, A. P.; Holgate, S. T.

BACKGROUND: LTC4 synthase is essential for the production of cysteinyl leukotrienes (Cys-LT), critical mediators in asthma. We have identified a novel promoter polymorphism at position -1072 (G/A) and a -444 (A/C) polymorphism has previously been reported. The role of these polymorphisms in the genetic susceptibility to asthma was examined. METHODS: To test for genetic association with asthma phenotypes, 341 white families (two asthmatic siblings) and 184 non-asthmatic control subjects were genotyped. Genetic association was assessed using case control and transmission disequilibrium test (TDT) analyses. LTC4S promoter luciferase constructs and transiently transfected human HeLa and KU812F cells were generated to determine the functional role of these polymorphisms on basal transcription. RESULTS: No associations were observed in case control analyses (-1072 A, q=0.09; -444 C, q=0.29); the TDT identified a borderline association between the -444 C allele and bronchial responsiveness to methacholine (p=0.065). Asthmatic children with the -444 C allele had a lower mean basal forced expiratory volume in 1 second (97.4 v 92.7\% predicted, p=0.005). LTC4S promoter luciferase analyses provided no evidence for a functional role of either polymorphism in determining basal transcription. CONCLUSION: This study does not support a role for these polymorphisms in genetic susceptibility to asthma but provides evidence to suggest a role in determining lung function parameters.

Allelic association and functional studies of promoter polymorphism in the leukotriene C4 synthase gene (LTC4S) in asthma / I., Sayers; S., Barton; S., Rorke; Beghe', Bianca; B., Hayward; P., Van Eerdewegh; T., Keith; J. B., Clough; S., Ye; J. W., Holloway; A. P., Sampson; S. T., Holgate. - In: THORAX. - ISSN 0040-6376. - ELETTRONICO. - 58(2003), pp. 417-424.

Data di pubblicazione:	2003
Titolo:	Allelic association and functional studies of promoter polymorphism in the leukotriene C4 synthase gene (LTC4S) in asthma.
Autore/i:	I., Sayers; S., Barton; S., Rorke; Beghe', Bianca; B., Hayward; P., Van Eerdewegh; T., Keith; J. B., Clough; S., Ye; J. W., Holloway; A. P., Sampson; S. T., Holgate
Autore/i UNIMORE:	I. Sayers S. Barton S. Rorke BEGHE', Bianca B. Hayward P. Van Eerdewegh T. Keith J. B. Clough S. Ye J. W. Holloway A. P. Sampson S. T. Holgate mostra contributor esterni nascondi contributor esterni
Rivista:	THORAX
Volume:	58
Pagina iniziale:	417
Pagina finale:	424
Codice identificativo ISI:	WOS:000182579900011
Codice identificativo Scopus:	2-s2.0-0038366908
Codice identificativo Pubmed:	12728163
Citazione:	Allelic association and functional studies of promoter polymorphism in the leukotriene C4 synthase gene (LTC4S) in asthma / I., Sayers; S., Barton; S., Rorke; Beghe', Bianca; B., Hayward; P., Van Eerdewegh; T., Keith; J. B., Clough; S., Ye; J. W., Holloway; A. P., Sampson; S. T., Holgate. - In: THORAX. - ISSN 0040-6376. - ELETTRONICO. - 58(2003), pp. 417-424.
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