Abstract
BackgroundEndotoxins stimulate T helper 1 cell maturation and send a negative signal to T helper 2 polarisation. This causes a decrease IgE levels and prevents atopy (Hygiene hypothesis). It is shown that this response is under genetic control by polymorphisms in CD14 and TLR4 genes in some researchs. We aimed to investigate the effects of genetic variants of CD14 (−) and TLR4 (Asp299Gly, Thr399Ile) genes on asthma phenotypes in adults with asthma.MethodsAsthma patients (n = 131) and healthy control cases (n = 75) were included in the study. Relations between CD14 C-159 T, TLR4 299 and TLR4 399 genotypes and duration of asthma history of allergic rhinitis-dermatitis, total IgE, eosinophil, skin prick test, forced expiratory volume 1 (FEV1) and severity of disease were evaluated. Real time PCR (RT-PCR) was used for genotyping.ResultsFor CD14-159, presence of the C allele (CC + CT) was more frequent among those with low median log (logarithm) IgE levels, but no statistically significant difference in all asthma group (p = 0.09). C allele was significantly correlated with low total IgE levels and T allele with high total IgE levels in atopics (p = 0.04). CC + CT genotype was more frequent in moderate and severe asthma group in atopics (p = 0.049). TLR4 299 and TLR4 399 genotypes and asthma phenotypes were not found to be significantly correlated (p > 0.05).ConclusionsTotal IgE levels were found to be low among patients with the CC + CT genotype, and high among patients with the TT genotype contrary to the results of many other studies, which is therefore an important finding. Another important finding was that the C allele is a risk factor for moderate and severe asthma.
Highlights
Endotoxins stimulate T helper 1 cell maturation and send a negative signal to T helper 2 polarisation
We investigated the effects of genetic variants of the CD14(C-159 T) and TLR4 (Asp299Gly and Thr399Ile) polymorphisms on adult asthma phenotypes the severity of disease, total IgE concentrations and eosinophil counts
CD14 C159 T, TLR4 299 and TLR4 399 genotypes, total IgE levels, eosinophil counts, and forced expiratory volume 1 (FEV1) were evaluated according to severity of disease and atopy status (Tables 4 and 5)
Summary
Endotoxins stimulate T helper 1 cell maturation and send a negative signal to T helper 2 polarisation This causes a decrease IgE levels and prevents atopy (Hygiene hypothesis). The TLR4 single nucleotide polymorphisms A896G and C1196T (result in the amino acid substitutions Asp299Gly → RefSNP ID: rs4986790 and Thr399Ile → RefSNP ID: rs4986791, respectively) and affect the extracellular domain of the TLR4 receptor [7,11] These two polymorphisms modify the receptor’s response to endotoxin, which is an important trigger of asthma [7]. We investigated the effects of genetic variants of the CD14(C-159 T) and TLR4 (Asp299Gly and Thr399Ile) polymorphisms on adult asthma phenotypes the severity of disease, total IgE concentrations and eosinophil counts. This study is important because it is the first to evaluate together with the effects of both CD14 and TLR4 genetic variants on disease in adult patients with asthma in Turkey
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