PMID: identifier of
Pubmed reference: |
 |
 (19096003) |
|
| title: |
|
CD14 and toll-like receptor gene polymorphisms, country living, and asthma in adults. |
|
| author(s): |
|
Lidwien Smit1, 2, Valérie Siroux3, Emmanuelle Bouzigon4, 5, Marie-Pierre Oryszczyn1, Mark Lathrop6, Florence Desmenais4, 5, Francine Kauffmann ( ) 1, For the EGEA collaboration(s) |
|
| laboratory: |
|
|
|
| short title : |
|
CD14, TLR2, rural living and asthma |
|
| abstract: |
|
RATIONALE: It has been shown that country living protects against asthma, which may be explained by microbial exposures. OBJECTIVES: To study whether single nucleotide polymorphisms (SNPs) in CD14 and Toll-like receptor (TLR) 2, TLR4 and TLR9 genes are associated with asthma in adults, and whether these SNPs modify associations between country living and asthma. METHODS: Twenty-five SNPs in CD14, TLR2, TLR4, and TLR9 genes were genotyped in adult subjects from the French Epidemiological study on the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy (EGEA). We conducted a case-control analysis on unrelated subjects (239 with asthma and 596 without asthma), and a family-based association test (FBAT) in 192 families ascertained through probands with asthma. MEASUREMENTS AND MAIN RESULTS: The TLR2/+596 C allele was associated with an increased risk for asthma in both case-control and family-based analyses (under a dominant model, odds ratio [OR] 1.91 and 95% confidence interval [CI] 1.34-2.72, P = 0.0003; Z statistics from FBAT = 2.48, P = 0.01). In skin prick test (SPT) positive subjects, the CD14/-260 C allele was negatively associated with asthma (additive model, OR 0.66; CI 0.48-0.91). Significant gene-environment interactions between variation in CD14 and TLR genes and country living during childhood were found for ten SNPs. In SPT positive subjects carrying CD14/-260 CC, country living protected against asthma (OR, 0.32; 95% CI, 0.12-0.85), whereas country living was not associated with asthma in subjects who were atopic and carrying CD14/-260 T (OR, 1.11; 95% CI, 0.65-1.90) (gene-environment interaction, P < 0.05). CONCLUSIONS: TLR2 and CD14 SNPs were associated with asthma and atopic asthma respectively. In addition, CD14, TLR2, TLR4, and TLR9 SNPs modified associations between country living and asthma. |
|
| subject: |
|
Life Sciences/Health Care Sciences and Epidemiology
|
|
| fulltext language: |
|
English |
|
| ISSN: |
|
1073-449X |
|
|
| publication format: |
|
Article in peer-reviewed journal |
|
| DOI: |
|
10.1164/rccm.200810-1533OC |
|
| journal: |
|
| American Journal of Respiratory and Critical Care Medicine (Am J Respir Crit Care Med) |
| Publisher |
American Thoracic Society |
| ISSN |
1073-449X (eISSN : 1535-4970) |
|
|
| Audience: |
|
international |
|
| publication date: |
|
2009-03-01 |
|
| submission date: |
|
2008-12-18 |
|
| volume: |
|
179 |
|
| issue: |
|
5 |
|
| page, identifiant, ...: |
|
363-8 |
|
|
| keyword(s) of author: |
|
asthma – atopy – epidemiology – gene-environment interaction – hygiene hypothesis |
|
| comment: |
|
3304 words |
|
| contract, financing: |
|
Funded by ANR-SEST, AFSSET. Lidwien Smit is supported by an EAACI-GA2LEN exchange fellowship award. |
|
