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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2011

Open Access 01-12-2011 | Research article

Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes

Authors: Nancy E Lange, Xiaobo Zhou, Jessica Lasky-Su, Blanca E Himes, Ross Lazarus, Manuel Soto-Quirós, Lydiana Avila, Juan C Celedón, Catherine M Hawrylowicz, Benjamin A Raby, Augusto A Litonjua

Published in: BMC Medical Genetics | Issue 1/2011

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Abstract

Background

Prior studies suggest a role for a variant (rs5743836) in the promoter of toll-like receptor 9 (TLR9) in asthma and other inflammatory diseases. We performed detailed genetic association studies of the functional variant rs5743836 with asthma susceptibility and asthma-related phenotypes in three independent cohorts.

Methods

rs5743836 was genotyped in two family-based cohorts of children with asthma and a case-control study of adult asthmatics. Association analyses were performed using chi square, family-based and population-based testing. A luciferase assay was performed to investigate whether rs5743836 genotype influences TLR9 promoter activity.

Results

Contrary to prior reports, rs5743836 was not associated with asthma in any of the three cohorts. Marginally significant associations were found with FEV1 and FVC (p = 0.003 and p = 0.008, respectively) in one of the family-based cohorts, but these associations were not significant after correcting for multiple comparisons. Higher promoter activity of the CC genotype was demonstrated by luciferase assay, confirming the functional importance of this variant.

Conclusion

Although rs5743836 confers regulatory effects on TLR9 transcription, this variant does not appear to be an important asthma-susceptibility locus.
Appendix
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Metadata
Title
Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes
Authors
Nancy E Lange
Xiaobo Zhou
Jessica Lasky-Su
Blanca E Himes
Ross Lazarus
Manuel Soto-Quirós
Lydiana Avila
Juan C Celedón
Catherine M Hawrylowicz
Benjamin A Raby
Augusto A Litonjua
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2011
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-12-26

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