Lydie Izakovičová Hollá

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 …

Association of 3 gene polymorphisms with atopic diseases

BACKGROUND Various peptidases, including angiotensin-converting enzyme (ACE), inactivate some inflammatory peptides that are considered to influence the pathogenesis of atopic diseases. This enzyme is also involved in the conversion or activation of 2 bronchoconstriction mediators: angiotensin II from angiotensinogen and endothelin (ET), respectively. OBJECTIVE We tested a hypothesis that asthma or other atopic diseases are associated with insertion/deletion ACE, M235T angiotensinogen, and TaqI ET-1 gene polymorphisms. METHODS A case-control approach was used in the study. Healthy subjects (141 persons) were used as control subjects, and 231 patients with histories of atopic asthma, allergic rhinitis, atopic dermatitis, or a combination thereof were studied. ACE genotype was determined by PCR, angiotensinogen M235T and ET-1 by PCR, and restriction analysis by AspI and TaqI, respectively. RESULTS We found the significant association of the insertion/deletion polymorphism of the ACE, as well as that of M235T polymorphism of the angiotensinogen genes, with the group of patients with atopic diseases ( P =.0025 and P =.0204, respectively). No difference was proved for the intron 4 (position 8000) polymorphism in the ET-1 gene when comparing the atopic patients with the control group (P =.1774). A significant difference was found between groups of patients with both asthma and rhinitis and patients without both respiratory atopic diseases (P =.0033). CONCLUSION It follows that the examined polymorphisms in the genes for ACE, angiotensinogen, and ET-1 could participate in the etiopathogenesis of atopic diseases.

Interactions of Lymphotoxin alpha (TNF-beta), Angiotensin-Converting Enzyme (ACE) and Endothelin-1 (ET-1) Gene Polymorphisms in Adult Periodontitis

BACKGROUND Adult periodontitis is a complex multifactorial disease whose etiology is not well defined. To investigate whether the genes encoded within the HLA class III region may confer susceptibility to periodontitis, polymorphisms in the ET-1 and TNF-β genes were analyzed together with the I/D polymorphism of the ACE gene. METHODS We determined allele and genotype frequencies of the NcoI bi-allelic polymorphism of the TNF-β gene, the I/D (insertion/deletion) polymorphism of the ACE gene, and the TaqI polymorphism of the ET-1 gene in 63 Caucasian patients with adult periodontitis and 95 orally healthy controls. RESULTS We found a significant difference in a 3 locus combination of genotypes between patients and controls (P <0.05). In the next analyses, no significant differences were found in allele frequencies of single genes, but we did find a significant difference in the genotype distribution between cases and controls for TNF-β (P <0.03). Differences were also observed for 2 locus combinations of ACE and TNF-β genotypes (P <0.03), and the ET-1 and TNF-β (P <0.05) genes. Evidence of deviation from Hardy-Weinberg equilibrium was observed in the periodontitis group for TNF-β, with an absence of the B1 B1 homozygotes in patients. CONCLUSIONS This study is of an exploratory nature. Considering the number of significant results, however, at least a part of the observed associations may obviously be real and our findings suggest that interactions of the TNF-β, ET-1, and ACE genes may be involved in susceptibility to adult periodontitis. J Periodontol 2001;72:85-89.

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.

Polymorphisms of the GSTM1 and GSTT1 genes in patients with allergic diseases in the Czech population.

Background:  Allergic diseases belong to the most common chronic disorders affecting mankind and their prevalence in population is increasing. Several studies have indicated that oxidative stress impairs pulmonary function and makes existing asthma worse. Members of the glutathione‐S‐transferase (GST) superfamily of genes are important in protection of cells from reactive oxygen species.

Polymorphisms of glutathione S-transferase M1, T1 and P1 in patients with reflux esophagitis and Barrett’s esophagus

AbstractReflux esophagitis (RE) and Barretts esophagus (BE) belong to the most common esophageal complications of gastroesophageal reflux disease. Glutathione S-transferase (GST) enzymes play an important role in cellular protection against oxidative stress and toxic foreign chemicals. Therefore, we investigated the hypothesis that polymorphisms in genes for these detoxifying enzymes could influence susceptibility to RE and BE. GSTM1, GSTT1 and GSTP1 loci were analyzed by PCR-based methods in 64 patients with RE (and an additional group of 22 subjects with BE as the fourth grade of esophagitis) and 173 unrelated controls. There were no significant differences in the distributions of GSTM1 and GSTT1 genotypes between the controls and patients with RE or BE. Similarly, frequencies of GSTP1 alleles were non-significantly different between the control and RE groups. However, GSTP1 B allele carriers were more frequent among the patients with BE compared to those in the reflux esophagitis group (P = 0.04, OR = 2.10, 95% CI 0.99-4.44) and most significantly when compared to the controls (P = 0.0067, Pcorr < 0.05, OR = 2.56, 95%CI 1.30-5.05). Although the GSTM1 and GSTT1 genes did not show any relationship with reflux disease, the GSTP1 gene might be one of the risk factors associated with susceptibility to RE, especially to BE.

Association of Toll-like receptor 9 haplotypes with chronic periodontitis in Czech population.

AIM Toll-like receptors (TLRs) belong to the pattern recognition receptors family of signal molecules that recognize conserved microbial structures. The aim of this study was to analyse polymorphisms in the TLR genes and their association with chronic periodontitis (CP). MATERIAL AND METHODS Two polymorphisms (2408G/A, i.e. Arg753Gln and -16934A/T) in TLR-2 and three variants (-1486C/T, -1237C/T and+2848A/G) in the TLR-9 genes were studied in 222 patients with CP and 259 unrelated controls. All polymorphisms were detected using the polymerase chain reaction-restriction fragment length polymorphism methods. Subgingival bacterial colonization was investigated by the VariOr Dento test. RESULTS No significant differences were found in allele and genotype frequencies of all polymorphisms between patients and controls. Nevertheless, complex analysis revealed differences in TLR9 haplotype frequencies between both groups (p=0.001). Specifically, the haplotype T(-1486)/T(-1237)/A(2848) was significantly more frequent (9.6%versus 2.8%, p<0.000001) and the haplotype T(-1486)/T(-1237)/G (2848) of the TLR9 gene was less frequent (35.9%versus 43.3%, p=0.01) in patients than in controls. However, no significant relationships between periodontal pathogens, TLR polymorphisms and CP were found. CONCLUSIONS In conclusion, although no significant role of the TLR2 gene in periodontitis was found, our results indicate that TLR9 haplotypes may be associated with susceptibility to CP.

Two MMP-2 promoter polymorphisms (-790T/G and -735C/T) in chronic heart failure

Abstract Remodelling of extracellular matrix by activated matrix metalloproteinases is considered to contribute to progression of ventricle remodelling during chronic heart failure. The aim of this study was to associate two promoter polymorphisms, -790T/G and -735C/T, in the gene for matrix metalloproteinase (MMP)-2 (gelatinase A) with chronic heart failure (CHF). For this purpose, 164 patients (124 men, 40 women, median age 56 years, range 21-91 years) with CHF (functional class NYHA II-IV, ejection fraction median 25%, cardiothoracic index more than 50%) were compared with 196 control subjects without clinical signs of cardiovascular disease (131 men and 65 women, median age 56 years, range 27-84 years) in -790T/G and -735C/T MMP-2 genotype distributions and allelic frequencies. The genotypes were determined by polymerase chain reaction (PCR) with restriction analyses. A significant increase of the T allele of the -790T/G MMP-2 polymorphism (p = 0.04), as well as of the C allele of the -735C/T MMP-2 gene polymorphism, in patients with CHF was proven (p = 0.04). The heterozygote CT of the 735C/T MMP-2 polymorphism exhibits a 7 times higher odds ratio (OR) for the CHF patients with lower levels of total cholesterol (less than 5 mmol/l), especially for nonhypertensive CHF men (OR = 7.28, 95% confidence interval 1.51-35.03, p = 0.006). Determination of MMP polymorphisms in the regulatory area of the gene could help us to comprehend individual susceptibility of patients with CHF to MMP inhibitors based on known risks of MMP genotypes. Clin Chem Lab Med 2003; 41(10):12991303

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.