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

BMC Medical Genetics

Research Article

Blanca E Himes¹  Jessica Lasky-Su¹  Ross Lazarus¹  Augusto A Litonjua²  Benjamin A Raby²  Nancy E Lange²  Xiaobo Zhou²  Catherine M Hawrylowicz³  Juan C Celedón⁴  Lydiana Avila⁵  Manuel Soto-Quirós⁵ 

[1] Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, 02115, Boston, MA, USA;Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, 02115, Boston, MA, USA;Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, 02115, Boston, MA, USA;Department of Asthma, Allergy and Respiratory Science, King's College London, Guy's Hospital, Great Maze Pond, SE1 9RT, London, UK;Division of Pediatric Pulmonary Medicine, Allergy and Immunology, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, One Children's Hospital Drive, 4401 Penn Ave., 15224, Pittsburgh, PA, USA;Division of Pediatric Pulmonology, Hospital Nacionál de Niños, Calle 20, San José, Costa Rica;

关键词: Asthma;    Single Nucleotide Polymorphism;    Population Stratification;    Nedocromil;    Allergic Bronchopulmonary Aspergillosis;   

DOI  :  10.1186/1471-2350-12-26

 received in 2010-08-04, accepted in 2011-02-15,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundPrior 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.Methodsrs5743836 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.ResultsContrary 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.ConclusionAlthough rs5743836 confers regulatory effects on TLR9 transcription, this variant does not appear to be an important asthma-susceptibility locus.

【 授权许可】

CC BY   
© Lange et al; licensee BioMed Central Ltd. 2011