Genetic variations in the human gelatinase A (matrix metalloproteinase-2) promoter are not associated with susceptibility to, and severity of, chronic periodontitis.

Background: Gelatinase A (matrix metalloproteinase-2 [MMP-2]) has been shown to play an important role in the pathogenesis of several disorders, including periodontal diseases. In this study, we test the hypothesis that variations in this gene influence the development and severity of chronic periodontitis.

Methods: Four promoter polymorphisms (-1575G/A, -1306C/T, -790T/G, and -735C/T) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods in 149 patients with mild to severe chronic periodontitis and 127 age-matched controls in the Czech population.

Endothelin-1 gene polymorphism in patients with malignant arrhythmias.

The endothelins are peptides with vasoconstricting and growth-promoting properties. Endothelin-1 (ET-1) is known with its direct positive inotropic and chronotropic effects on isolated heart and with growth effects. The aim of this pilot study was to investigate the frequency distribution of the common polymorphism of the ET-1 gene and its possible relation with hemodynamic consequences of malignant ventricular arrhythmias in patients with structural heart disease.

Analysis of the interleukin-6 gene promoter polymorphisms in Czech patients with chronic periodontitis.

Background: Chronic periodontitis is an inflammatory disease, which is a major cause of tooth loss. The proinflammatory cytokines interleukin-1 (IL-1) and interleukin-6 (IL-6) are key regulators of the host response to microbial infection and major modulators of extracellular matrix catabolism and bone resorption. The purpose of this study was to investigate the associations of chronic periodontitis with IL-6 gene polymorphisms (at positions -597 [G/A], -572 [G/C], and -174 [G/C]).

A haplotype constituted of four MMP-2 promoter polymorphisms (-1575G/A, -1306C/T, -790T/G and -735C/T) is associated with coronary triple-vessel disease.

Vascular lesion development is associated with an accumulation of extracellular matrix proteins within the vessel wall. The proteins are degraded by matrix metalloproteinases (MMPs). There is also evidence indicating a participation of the MMPs in the weakening of atherosclerotic plaque that predisposes to lesion disruption.

Three novel polymorphisms in the promoter region of the TIMP-3 gene are not associated with proliferative diabetic retinopathy in type 2 diabetes mellitus.

Purpose: Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a member of the TIMP family of proteins, playing a significant role in the control of extracellular matrix remodelling. TIMP-3 might play a role in the regulation of retinal neovascularization during progression of diabetic retinopathy. Recently, three novel polymorphisms (-899T/A, -915A/G and -1296T/C) in the promoter region of the TIMP-3 gene have been identified.

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

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.

C766T low-density lipoprotein receptor-related protein 1 (LRP1) gene polymorphism and susceptibility to breast cancer.

Background: Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor with an important role in regulating the activity of proteinases in extracellular matrix. Several studies have also described its role in intracellular signaling. Previous studies showed that the expression of LRP1 is related to invasiveness of cancer cells.

I/D ACE gene polymorphism in survival of leukemia patients -- hypothesis and pilot study.

Angiotensin-I converting enzyme (ACE) is involved not only in intracellular volume regulation but also in proliferation control. Since both ACE gene polymorphism (I/D ACE) and ABO blood group determine ACE level in peripheral blood and probably also in bone marrow, the hypothesis to the interindividual differences in survival of leukemic patients was suggested. The data of 25 patients of both sexes with acute myelogenous (AML), acute lymphatic (ALL), chronic myelogenous (CML) and chronic lymphatic (CLL) leukemia treated by conventional were used for the study.

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

Over 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.

Association of two angiotensinogen gene polymorphisms, M235T and G(-6)A, with chronic heart failure.

The aim of the study was to focus on the relationship between the angiotensinogen (AGT) gene polymorphisms, M235T and promoter G(-6)A, and chronic heart failure in the Czech population. A total of 158 patients with chronic heart failure (functional class NYHA II-IV, ejection fraction <40%, cardiothoracic index >50%) were compared with a control group of 200 subjects of similar age and sex distribution, without any personal history of cardiovascular diseases. The AGT gene polymorphisms were detected by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods.

Genetic variation in the promoter region of the basic fibroblast growth factor gene.

Basic fibroblast growth factor (bFGF) is a member of the fibroblast growth factor family that possess broad mitogenic and cell survival activities and is involved in a variety of biological processes. We investigated possible genetic polymorphism in the promoter and 5' flanking region of the bFGF gene. Polymorphism was analysed by means of heteroduplex analysis, fragments with altered mobility were sequenced.

Lack of association between atopic asthma and the tumor necrosis factor alpha-308 gene polymorphism in a Czech population.

Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components. Several investigators have linked the tumor necrosis factor (TNF) genes and nearby markers located on chromosome 6p to atopy and asthma. A recent study has demonstrated that the TNF-alpha*2 allele of a polymorphism in the TNF-alpha gene promoter region (G-308 A) is associated with a higher risk for the development of atopy in Spanish patients.

Endothelin-1 gene polymorphism in the identification of patients at risk for malignant ventricular arrhythmia.

Background: The endothelins are peptides with vasoconstricting and growth-promoting properties. Endothelin-1 (ET-1) is known for its direct positive inotropic and chronotropic effects on isolated heart, and for growth effects. The aim of this pilot study was to investigate the frequency distribution of a common polymorphism of the endothelin (ET-1) gene and its possible relation to the hemodynamic consequences of malignant ventricular arrhythmia in patients with structural heart disease.

Drugs elevating extracellular adenosine promote regeneration of haematopoietic progenitor cells in severely myelosuppressed mice: their comparison and joint effects with the granulocyte colony-stimulating factor.

We tested capabilities of drugs elevating extracellular adenosine and of granulocyte colony-stimulating factor (G-CSF) given alone or in combination to modulate regeneration from severe myelosuppression resulting from combined exposure of mice to ionizing radiation and carboplatin. Elevation of extracellular adenosine was induced by joint administration of dipyridamole (DP), a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), serving as an adenosine prodrug. DP+AMP, G-CSF or all these drugs in combination were administered in a 4-d treatment regimen starting on day 3 after induction of myelosuppression.

Polymorphism R25P in the gene encoding transforming growth factor-beta (TGF-beta1) is a newly identified risk factor for proliferative diabetic retinopathy.

Associations of the genetic polymorphisms in the promoter region and the signal peptide sequence of the transforming growth factor-beta (TGF-beta1) gene with proliferative diabetic retinopathy (PDR) in patients with non-insulin-dependent diabetes mellitus (NIDDM) were studied. A total of 245 Caucasian subjects comprised the two groups: NIDDM patients with PDR (n = 73) and NIDDM patients without PDR (n = 172). Allele frequencies of common TGF-beta1 polymorphisms (at positions -988C/A, -800G/A, -509C/T, +869T/C (L10P), and +915G/C (R25P)) were determined by PCR-based methodology.

The relationship among apolipoprotein(a) polymorphisms, the low-density lipoprotein receptor-related protein, and the very low density lipoprotein receptor genes, and plasma lipoprotein(A) concentration in the Czech population.

Increased plasma concentration of lipoprotein(a) [Lp(a)] is an established independent risk factor for coronary artery disease (CAD), which is strongly genetically determined. This study was designed to investigate the relationship between the K-IV and (TTTTA)n apolipoprotein(a) [apo(a), protein; APOA, gene] polymorphisms, as well as the C766T low-density lipoprotein receptor-related protein (LRP) and the (CGG)n very low density lipoprotein receptor (VLDLR) polymorphisms on the one hand, and plasma Lp(a) levels in Czech subjects who underwent coronary angiography on the other hand. The lengths of the alleles of the APOA K-IV and (TTTTA)n polymorphisms were strongly inversely correlated with plasma Lp(a) levels in univariate analysis (r = -0.

Association of three polymorphisms in the gene coding for endothelin-1 with essential hypertension, overweight and smoking.

Objective: To evaluate the association of three endothelin-1 (ET-1) gene polymorphisms with essential hypertension, as well as with two cardiovascular risk factors: body mass index (BMI) and smoking.

Design: Three gene polymorphisms and the genotype and allelic distributions were compared between normotensive healthy volunteers and patients with essential hypertension. The genetic association of the three genotypes with BMI and smoking status was calculated.

Interactions of Lymphotoxin α (TNF-β), 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.