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The effect of CD14 and TLR4 gene polymorphisms on asthma phenotypes in adult Turkish asthma patients: a genetic study.

Sahin F, Yıldız P, Kuskucu A, Kuskucu MA, Karaca N, Midilli K - BMC Pulm Med (2014)

Bottom Line: This causes a decrease IgE levels and prevents atopy (Hygiene hypothesis).TLR4 299 and TLR4 399 genotypes and asthma phenotypes were not found to be significantly correlated (p > 0.05).Total 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Chest Diseases, Yedikule Chest Diseases and Surgery Training and Research Hospital, Zeytinburnu/İstanbul, 34760, Turkey. fusunsahin19700@hotmail.com.

ABSTRACT

Background: 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). 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.

Methods: Asthma 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.

Results: For 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).

Conclusions: Total 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.

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The association between the severity of asthma and CC+CT and TT genotypes in all asthma patients and atopic asthma group. A-The insignificant association between the severity of asthma and CC + CT and TT genotypes in all asthma patients (p = 0.10). B-The significant association between the severity of asthma and CC + CT and TT genotypes in atopic asthma group (p = 0.049).
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Figure 2: The association between the severity of asthma and CC+CT and TT genotypes in all asthma patients and atopic asthma group. A-The insignificant association between the severity of asthma and CC + CT and TT genotypes in all asthma patients (p = 0.10). B-The significant association between the severity of asthma and CC + CT and TT genotypes in atopic asthma group (p = 0.049).

Mentions: Total IgE levels were converted to a normal distribution using logarithmic (log) transformation. No significant difference was observed when individually comparing the median log IgE (according to 1.99) among patients with the CC, CT, TT genotypes of the CD14C-159 T polymorphism (p = 0.08); in the asthma group, presence of the C allele (CC + CT) was more frequent among those with low IgE levels, but no statistically significant difference was detected (p = 0.09, Figure 1A). Patients in the asthma group were classified as either atopic and non-atopic according to the results of the skin prick test and history of atopic rhinitis-dermatitis A significant association was observed between skin prick test positivity and high total IgE levels and eosinophil counts. Moderate asthma was more frequent in the atopic group and severe asthma was found in the non-atopic group; FEV1 was lower in both the atopic and non-atopic groups. In atopic patients, there was a significant association between the median log IgE (according to 1.99) and the presence of the C allele (p = 0.04, Figure 1B). As a result, it was found that the C allele was significantly correlated with low total IgE levels and that the T allele was significantly correlated with high total IgE levels. However, among all asthma patients, no significant association was observed between the severity of asthma and CC + TT and TT (p = 0.10, Figure 2A). In the atopy group, a significant association was also observed between the severity of asthma and CC + TT and TT genotypes (p = 0.049, Figure 2B). Specifically, the C allele was significantly more frequent in the moderate and severe asthma groups.


The effect of CD14 and TLR4 gene polymorphisms on asthma phenotypes in adult Turkish asthma patients: a genetic study.

Sahin F, Yıldız P, Kuskucu A, Kuskucu MA, Karaca N, Midilli K - BMC Pulm Med (2014)

The association between the severity of asthma and CC+CT and TT genotypes in all asthma patients and atopic asthma group. A-The insignificant association between the severity of asthma and CC + CT and TT genotypes in all asthma patients (p = 0.10). B-The significant association between the severity of asthma and CC + CT and TT genotypes in atopic asthma group (p = 0.049).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928321&req=5

Figure 2: The association between the severity of asthma and CC+CT and TT genotypes in all asthma patients and atopic asthma group. A-The insignificant association between the severity of asthma and CC + CT and TT genotypes in all asthma patients (p = 0.10). B-The significant association between the severity of asthma and CC + CT and TT genotypes in atopic asthma group (p = 0.049).
Mentions: Total IgE levels were converted to a normal distribution using logarithmic (log) transformation. No significant difference was observed when individually comparing the median log IgE (according to 1.99) among patients with the CC, CT, TT genotypes of the CD14C-159 T polymorphism (p = 0.08); in the asthma group, presence of the C allele (CC + CT) was more frequent among those with low IgE levels, but no statistically significant difference was detected (p = 0.09, Figure 1A). Patients in the asthma group were classified as either atopic and non-atopic according to the results of the skin prick test and history of atopic rhinitis-dermatitis A significant association was observed between skin prick test positivity and high total IgE levels and eosinophil counts. Moderate asthma was more frequent in the atopic group and severe asthma was found in the non-atopic group; FEV1 was lower in both the atopic and non-atopic groups. In atopic patients, there was a significant association between the median log IgE (according to 1.99) and the presence of the C allele (p = 0.04, Figure 1B). As a result, it was found that the C allele was significantly correlated with low total IgE levels and that the T allele was significantly correlated with high total IgE levels. However, among all asthma patients, no significant association was observed between the severity of asthma and CC + TT and TT (p = 0.10, Figure 2A). In the atopy group, a significant association was also observed between the severity of asthma and CC + TT and TT genotypes (p = 0.049, Figure 2B). Specifically, the C allele was significantly more frequent in the moderate and severe asthma groups.

Bottom Line: This causes a decrease IgE levels and prevents atopy (Hygiene hypothesis).TLR4 299 and TLR4 399 genotypes and asthma phenotypes were not found to be significantly correlated (p > 0.05).Total 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Chest Diseases, Yedikule Chest Diseases and Surgery Training and Research Hospital, Zeytinburnu/İstanbul, 34760, Turkey. fusunsahin19700@hotmail.com.

ABSTRACT

Background: 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). 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.

Methods: Asthma 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.

Results: For 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).

Conclusions: Total 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.

Show MeSH
Related in: MedlinePlus