CD14 and toll-like receptor gene polymorphisms, country living, and asthma in adults.
BACKGROUND
It has been shown that country living protects against asthma, which may be explained by microbial exposures.


OBJECTIVE
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.


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.
Smit
Lidwien A M
LA
INSERM U780, Villejuif, France.
Siroux
Valérie
V
Bouzigon
Emmanuelle
E
Oryszczyn
Marie-Pierre
MP
Lathrop
Mark
M
Demenais
Florence
F
Kauffmann
Francine
F
D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D004781:Environmental Exposure; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000276:immunology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012423:Rural Health; D051193:Toll-Like Receptors / Q000235:genetics* / Q000276:immunology
D018950:Lipopolysaccharide Receptors; D051193:Toll-Like Receptors