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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-12

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

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. More... »

PAGES

26

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2350-12-26

DOI

http://dx.doi.org/10.1186/1471-2350-12-26

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042800997

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21324137


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