Dana Bučková

Two CD14 promoter polymorphisms and atopic phenotypes in Czech patients with IgE-mediated allergy.

Background: Immunoglobulin E (IgE)‐mediated allergy belongs to common chronic disorders resulting from an interaction between both genetic and environmental factors. The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localized on chromosome 5q31.1, a region that is linked to asthma and bronchial hyperresponsiveness. Recently, several polymorphisms in the promoter region of this gene have been associated with atopic phenotypes in various populations.

Promoter polymorphisms in the CD14 receptor gene and their potential association with the severity of chronic periodontitis

Periodontitis, a chronic inflammation of the tissues surrounding the teeth, is a common disease affecting all populations. The main aetiology remains a bacterial infection that leads to gingival inflammation, loss of alveolar bone, and tooth loss.1 Although the presence of pathogenic micro-organisms is required to trigger this process, the amplification and progression of the disease is believed to rely heavily on the production of host mediators in response to bacteria and/or their metabolic products.2 The CD14 molecule, described as the major endotoxin receptor, is one of the receptors which act on the recognition of lipopolysaccharides (LPS, endotoxin) and gram positive or mycobacterial cell wall components and thus can initiate the innate immune response to bacterial invasion.3–5 It is constitutively expressed primarily on the surface of monocytes, macrophages, neutrophils, and gingival fibroblasts (mCD14).6 In addition, a soluble form of CD14 (sCD14) is abundant in serum and is apparently derived both from the secretion of CD14 and from enzymatically cleaved glycosyl-phosphatidylinositol anchored mCD14.7 Besides the role of CD14 in the host defence, several other biological functions have been found. CD14 is involved in the phagocytosis of gram negative bacteria,8 LPS mediated bone resorption,9 and monocyte-endothelial cell interactions. Furthermore, changes in CD14 expression and serum sCD14 levels seem to be associated with a number of pathological states including periodontal diseases.10 CD14 production is genetically regulated. The gene for the CD14 receptor is on chromosome 5 (region q23-21), consists of ≈3900 bp organised in two exons, and encodes a protein of 375 amino acids.11 In the promoter region of the CD14 gene, a C to T transition was identified at position –159 upstream from the major transcription site, which is near to an SP1 binding site that has a major influence on the monocyte …

TGF-beta1 gene polymorphisms

Transforming growth factor beta (TGF-beta) is a pleiotropic cytokine with significant anti-inflammatory and immunosuppressive properties. The single base pair polymorphism located at -509 (C/T) in the promoter region of the TGF-beta1 gene was previously shown to be associated with elevated total serum IgE levels. We tested the hypothesis that polymorphic alleles of the TGF-beta1 gene are associated with allergies and asthma.

Prevalence of endothelial nitric oxide synthase gene polymorphisms in patients with atopic asthma

Background Asthma is a common multifactorial disease, the aetiology of which is attributable to both environmental and genetic factors. The endothelial nitric oxide synthase (NOS3) gene has been implicated in asthma pathogenesis.

Plasminogen-activator-inhibitor-1 promoter polymorphism as a risk factor for adult periodontitis in non-smokers

Periodontal diseases belong to the most common chronic disorders affecting mankind. Smoking and impaired plasminogen activation with hypercoagulation and fibrinolysis inhibition have been proposed as having a role in predisposition to these diseases. We investigated relationships among adult periodontitis, smoking, and a variation in the deletion/insertion (4G/5G) promoter polymorphism of the plasminogen-activator-inhibitor-1 (PAI-1) gene in 304 Caucasian subjects. An association was detected between the deletion (4G) allele (and 4G/4G genotype) and periodontitis (P = 0.0022, Pcorr < 0.01; P = 0.014, Pcorr < 0.05). A stronger association occurred in non-smokers (P = 0.00021, Pcorr < 0.01; P = 0.0024, Pcorr < 0.05) where the presence of the PAI-1 gene 4G allele appears to be one of the risk factors for periodontitis.

Polymorphisms of the CD14 gene and atopic phenotypes in Czech patients with IgE-mediated allergy

AbstractIgE-mediated allergy is a common chronic disorder resulting from interactions between genetic and environmental factors. The gene encoding CD14 is a positional candidate gene for allergic diseases as it is localised on chromosome 5q31.1, a region linked to asthma and bronchial hyperresponsiveness. We investigated the relationship among atopic phenotypes and six polymorphisms in the CD14 gene. Polymerase chain reaction with RFLP analyses was used to determine the CD14 genotypes in subjects with IgE-mediated allergic diseases (n=282) and random controls (n=187). No significant differences in allele or genotype frequencies for individual polymorphisms between patients and controls were found. However, when atopic patients were subdivided into subjects with positive and with negative skin prick tests for separate antigens, T allele of the 1341G/T polymorphism was significantly associated with positive reactivity to mites (P=0.007) and moulds (P=0.041). Similarly, the C allele frequency of the −159C/T variant was increased in patients with positive skin prick tests for mites (P=0.046) and moulds (P=0.056). In haplotype analysis, the common −1619A/−1359G/−550C/−159C/+1188G/+1341T haplotype was associated with positive reaction to these antigens (P values: 0.0008-0.0035). Our study supports the idea that CD14 plays a role in IgE-mediated allergic diseases, and its gene polymorphisms can be important for manifestation of these disorders.

Neuronal nitric oxide synthase gene polymorphism and IgE-mediated allergy in the Central European population

Background:  Several findings suggest that nitric oxide (NO) plays a significant role in the regulation of the Th1/Th2 balance and contributes to the development of allergic diseases. Our study investigates a possible association of C/T transition located 276‐bp downstream from the translation termination site in exon 29 of the human nitric oxide synthase type 1 (NOS1) gene with immunoglobulin E (IgE)‐mediated allergic diseases in the Czech population.

The role of the IKAP gene polymorphisms in atopic diseases in the middle European population

AbstractOver ten genome-wide screens and many candidate genes studies were performed worldwide to elucidate genetic factors involved in the pathogenesis of bronchial asthma and other atopic diseases. Results from these studies were often discordant, which might have reflected complexity and heterogeneity of these multifactorial diseases. Among a variety of other loci, specific variants of the gene for IKAP (IKK complex-associated protein) were shown to be associated with bronchial asthma in children in a Japanese study. To test the possible role of SNPs in the coding region of the IKAP gene in atopic asthma or other atopic phenotypes in a highly homogenous Czech population, a case-control study including 373 patients and 309 healthy control subjects was performed. There were no significant differences in the genotype and allele distributions for any of five SNPs in the IKAP gene (T819C, G2295A, A2490G, T3214A and C3473T) between patients with atopic asthma or other atopic diseases and healthy controls. These results suggest that the polymorphisms in the coding region of the IKAP gene are unlikely to contribute to atopic disease risk in the Czech population.