MicroRNAs in pathophysiology of acute myocardial infarction and cardiogenic shock.

AIM: Levels of circulating miRNA are considered to be potential biomarkers of acute myocardial infarction and disease progression. METHODS: In this study, the expression levels of circulating miRNA-1, miRNA-133 and miRNA-124a were investigated in a group of patients with acute myocardial infarction (STEMI) and cardiogenic shock (CS) compared to controls. RESULTS: During the hospitalization period, miRNA-133 showed a significant up-regulation in the serum of STEMI and CS patients compared to controls, while the expression of miRNA-1 was significantly different only in CS. The expression of miRNA-124 was significantly higher in STEMI and CS. Furthermore, miRNA-1 expression was related to the level of circulating glucose in patients with STEMI. We also found a negative correlation between miRNA-133 and MMP-9 levels. MiRNA-124 expression was significantly related to the level of soluble ST2; the marker correlated to cardiac damage. CONCLUSION: All selected miRNAs are potential markers of cardiac injury in cardiogenic shock, whereas miRNA-124a and -133 are markers of injury in STEMI. MiRNA-1 expression is related to circulating glucose in STEMI. None of miRNAs could be correlated to the extent of injury, progress of the disease, or prognosis of patient outcome. Therefore, the levels of circulating miRNA have no potential for becoming a biomarker of myocardial damage and as such would bring no further benefit compared to current markers (Tab. 4, Fig. 1, Ref. 47).

Genetic predisposition for chronic venous insufficiency in several genes for matrix metalloproteinases (MMP-2, MMP-9, MMP-12) and their inhibitor TIMP-2.

OBJECTIVE: The project was scheduled as a case-control study to investigate the correlation between MMP-2 (rs243864), MMP-9 (3918242), MMP-12 (rs7123600) and TIMP-2 (rs8176329) polymorphisms and chronic venous disease (CVD) risk. The genotype and phenotype research envisages the testing of possible associations between MMP and TIMP-2 genotypes and phenotypes of CVD. MATERIAL AND METHODS: 150 patients with CVD and 227 controls were enrolled into the study. The MMPs and TIMP-2 genotypes were identified by the PCR method and restriction analysis according to standard protocols. RESULTS: The G allele of MMP-2 -790 T/G was 1.85 times more frequent in men with CVD than in the control group (P = 0.008). The T allele of MMP-9 -1562 C/T was observed 2.571 times more frequently in patients with CVD than in the control individuals (both in men and women) with clinically significant specificity (P = 0.0000009). The G allele of MMP-12 rs7123600 was determined 2.082 times more frequently in female patients with CVD than in the control group with clinically significant specificity (P = 0.02). No significant result in TIMP-2 rs8176329 polymorphism in the case-control study was observed. CVD women with G allele in MMP-2 -790 T/G in the genotype-phenotype study are seen to develop ulceration 2.539 times more frequently (P = 0.003). The G allele of MMP-12 rs7123600 was detected 3.167 times more frequently in CVD women with ulceration compared with CVD women without ulceration (P = 0.007). In CVD men in C6 stage, the incidence of AG genotype in rs7123600 MMP-12 polymorphism was found to be 4.675 times higher compared to CVD women with C6 staging (P = 0.005). The AG genotype in TIMP 2 rs8176329 polymorphism was found to be associated with higher risk of tumour (P = 0.01). CONCLUSION: Studying these polymorphisms can contribute to better identification of patients at higher risk of developing CVD, while providing the most appropriate prevention and treatment strategies for limiting the progression and complications of CVD.

Relation of IL-6, IL-13 and IL-15 gene polymorphisms to the rheumatoid factors, anti-CCP and other measures of rheumatoid arthritis activity.

The aim of the study was to examine the relation between polymorphisms and serum levels of selected cytokines (IL-6, IL-13 and IL-15), production of autoantibodies and factors describing rheumatoid arthritis (RA), such as DAS28 and Total Sharp Score. A total of 156 patients with RA according to the ACR criteria, and 200 control subjects were recruited into the study. The measurements of CRP, anti-CCP, the presence of rheumatoid factors (RFs), radiographs of both hands with calculation of Total Sharp Score (TSS) and DAS28 were obtained from all patients with RA. In total, five polymorphisms in genes coding cytokines (IL-6, IL-13 and IL-15) were detected. The levels of these selected cytokines were measured in serum using ELISA method. A significant difference in allele frequencies between patients with RA and controls was observed for IL-15 -267C/T polymorphism. A higher prevalence of heterozygote variants of IL-15 polymorphisms (14035A/T and -267C/T) in the RF IgG- and RF IgA-negative subgroups was observed. Furthermore, the association of polymorphisms in gene for IL-15 with circulating level of IL-15 (14035A/T and 367G/A) and with total RF and Ig-specific RFs (-267C/T) was found. The relation of IL-15 to RFs IgA, IgM, IgG and the measure of DAS28 was proved. The frequency of the T allele of the IL-13 polymorphism -1112C/T was higher in subgroup with faster progression of the disease (TSS/month ≥ 0.1). In conclusion, we present an association of IL-15 gene polymorphisms with the RFs including subtypes (RF, IgG, IgA) underlined by the relation of increased IL-15 levels in circulation to RFs.

Brain-derived neurotrophic factor and ciliary neurotrophic factor in maternal plasma and umbilical cord blood from pre-eclamptic and physiological pregnancies.

The aim of the study was to investigate the circulating levels of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in maternal serum and umbilical cord blood from respective pregnancies in pre-eclampsia (PE) cases and a control cohort. A total of 12 pre-eclampsia cases and 34 healthy controls were enrolled and the maternal peripheral blood - umbilical cord blood duos, were examined for BDNF and CNTF levels. BNDF levels were significantly higher in umbilical cord blood from pre-eclamptic pregnancies; there was also significant difference between maternal plasma and umbilical cord blood levels of BDNF (p < 0.001) in the controls. The CNTF levels in umbilical cord blood (CNTF-UCB) were significantly higher in PE cases than in the controls (p = 0.03). Significant differences were observed in expression of BDNF and CNTF proteins in maternal peripheral blood and umbilical cord blood between pre-eclampsia cases and healthy controls.

[Adrenocorticotropin hormone--possible marker of pregnancy pathologies]. / Kortikotropin-releasing hormon a adrenokortikotropní hormon--mozné markery nekterých tehotenských patologií.

Adrenocorticotropin hormone (ACTH) is produced from the anterior pituitary gland and can be considered as one of the main elements of the hypothalamic-pituitary-adrenal axis. ACTH secretion is controled by corticotropin-releasing hormone (CRH) from hypothalamus. ACTH stimulates the adrenal cortex. It's affects synthesis and releasing of glucocorticoids, precursors of aldosterone, which affects the synthesis of mineralocorticoids. Preeclampsia and intrauterine growth retardation (IUGR) is one of the major pregnancy pathologies. The aetiology of these states are not clearly known, it is assumed that factors pathogenetic chain has been operating in early pregnancy. These factors are generally similar for both diseases. It is assumed that these pathologies will activate the hypothalamic-pituitary-adrenal stress axis both for mother and fetus. In research studies, mathernal plasma CRH concentrations are elevated in complicated pregnancies. Etiopathogenesis of severe pregnancy pathologies such as IUGR, or preeclampsia is still unclear. Therefore, the research focuses on finding new markers that contribute to early diagnosis of serious states.

Relationship of resistin levels with endometrial cancer risk.

Cancer of endometrium (CAE) is the most common gynecologic malignancy in industrialized nations. Increased resistin levels, an adipocytokine produced by adipose tissue and macrophages, have been considered as a risk factor in gastric, colon and breast cancer, recently. No studies associating resistin levels with endometrial cancer have been done so far. The purpose of this case-control study was to determine the relationship between serum circulating resistin levels and resistin gene -420C>G (rs3219175) variant in endometrial cancer patients. 37 Caucasian female patients and 39 healthy controls were enrolled in this study. Difference in resistin levels between age and BMI matched patients group (mean 24.2 ng/ml) and control subjects (mean 10.1 ng/ml) were statistically significant (p <001). We also determined single nucleotide polymorphism -420C>G (rs3219175) within resistin gene and no significant association between resistin levels and investigated polymorphism was found. Furthermore, no significant association between higher resistin levels and diabetes mellitus 2, body mass index, smoking or age have been observed within studied groups. To our knowledge, this is the first study examining the relationship between serum resistin levels and endometrial cancer and our results show, that patients with endometrial cancer have significantly increased circulating levels of resistin compared to control subjects.

Association of A1166C polymorphism in AT(1) receptor gene with baroreflex sensitivity.

The aim of this study was to evaluate the association of A1166C polymorphism in angiotensin II type 1 receptor (AT(1)R) gene with baroreflex sensitivity (BRS in ms/mm Hg; BRSf in mHz/mm Hg) in man. BRS and BRSf were determined by a spectral method in 135 subjects (19-26 years) at a frequency of 0.1 Hz. Genotypes were detected by means of polymerase chain reaction and restriction analysis using enzyme DdeI. We compared BRS and BRSf among genotypes of this polymorphism. The frequency of genotypes of AT(1)R A1166C polymorphism was: 45.9 % (AA, n=62), 45.9 % (AC, n=62), 8.2 % (CC, n=11). Differences in BRS (p<0.05) and BRSf (p<0.01) among genotypes of this single nucleotide polymorphism were found (Kruskal-Wallis: BRS - AA: 7.9+/-3.3, AC: 8.6+/-3.6, CC: 5.9+/-2.3 ms/mm Hg; BRSf - AA: 12.0+/-4.0, AC: 12.0+/-5.0, CC: 8.0+/-3.0 mHz/mm Hg). Compared to carriers of other genotypes (AA+AC) the homozygotes with the less frequent allele (CC) showed significantly lower BRSf (Mann-Whitney: BRSf - AA+AC: 12.0+/-4.0, CC: 8.0+/-3.0 mHz/mm Hg; p<0.01) and borderline lower BRS (BRS - AA+AC: 8.2+/-3.5, CC: 5.9+/-2.5 ms/mm Hg; p=0.07). We found a significant association of A1166C polymorphism in AT(1) receptor gene with baroreflex sensitivity. Homozygosity for the less frequent allele was associated with decreased baroreflex sensitivity.

Association of polymorphisms of zinc metalloproteinases with clinical response to stem cell therapy.

AIM: The purpose of this study was to assess the associations of polymorphisms in two metalloproteinase genes-metalloproteinase-2 (MMP-2) and angiotensin converting enzyme (ACE)-with clinical response to autologous transplantation of mononuclear bone marrow cells (MBMC) in patients with acute myocardial infarction. METHODS: The double centre study included 48 patients with a first acute myocardial infarction treated with primary coronary angioplasty, stent implantation and transplantation of MBMC. According to the changes in perfusion defect size, left ventricle ejection fraction, end-systolic volume and peak systolic velocity of the infracted wall (dSaMI) after cell therapy, the patients were retrospectively divided into group A (responders) and group B (non-responders). Genomic DNA was isolated from peripheral leukocytes by a standard technique using proteinase K. Three MMP-2 promoter (-1575G/A, -1306C/T and -790T/G) as well as I/D ACE gene polymorphisms were detected by PCR methods with restriction analyses (when necessary) according to standard protocols. RESULTS: Of the 48 patients who received MBMC transplantation, 17 responded to the therapy. There were no significant differences in the prevalence of matrix metalloproteinase-2 triple genotype GGCCTT between responder/non-responder groups (71% versus 61%, p=0.375). Similarly, no differences in either genotype distribution or allelic frequencies of I/D ACE polymorphism between responders and non-responders to the cell therapy were observed (p=0.933). Compared to patients with ACE genotype ID or DD, the patients with ACE II genotype significantly improved in regional systolic LV function of the infarcted wall after implantations of MBMC (dSaMI - 0.4 versus 1.4 cm/s, p=0.037). CONCLUSION: In our study, the ACE genotype II was associated with improvement of regional systolic LV function of the infarcted wall after implantations of MBMC. The detected polymorphism in matrix metalloproteinase-2 gene was not associated with clinical response to cell therapy.

Covid-19 infection and the host genetic predisposition: does it exist?

Knowledge of genomic interindividual variability could help us to explain why different manifestation of clinical severity of Covid-19 infection as well as modified pharmacogenetic relations can be expected during this pandemic condition.

Association of the eNOS 4a/b and -786T/C polymormphisms with coronary artery disease, obesity and diabetes mellitus.

The aim was to assess the relationship between eNOS 4a/b and -786T/C polymorphisms with coronary artery disease (CAD), obesity and diabetes mellitus. Total number of 1313 patients underwent coronary angiography, 939 had significant CAD (stenosis of > or = 1 coronary artery > or = 50%), 222 had smooth coronary arteries. Patients with insignificant atherosclerosis were excluded, the study finally comprised 1161 patients. The analysis of eNOS 4a/b and -786T/ C polymorphisms was performed by polymerase chain reaction. No significant interaction was found between -786T/C polymorphism and solitary CAD or CAD with diabetes and obesity. For 4a/b polymorphism, genotypes aa+ab were almost three times more frequent in diabetic patients without CAD versus patients without CAD and without diabetes--OR 2.79; P = 0.009, Pcorr = 0.03. In 4a/b polymorphism and CAD with obesity and diabetes: bb genotype was significantly more frequent: in patients with CAD, diabetes and obesity in comparison with obese diabetic patients without CAD (OR = 3.63, Pcorr = 0.05); in non-diabetic non-obese patients with CAD, versus diabetic and obese patients without CAD (OR = 3.38, Pcorr = 0.05); in obese non-diabetic patients without CAD vs. obese diabetic patients without CAD (OR = 5.91, Pcorr = 0.01); in patients without CAD, obesity and diabetes vs. obese diabetic patients without CAD (OR = 3.59, Pcorr = 0.05). The eNOS 4a/b polymorphism has significant association with diabetes mellitus in CAD-negative patients, and with CAD in combination with obesity and diabetes mellitus. No association between 4a/b or -786T/C polymorphism and solitary CAD was found.

The efficacy of magnesium sulfate on resolving surgically provoked vasospasm of the flap pedicle in an experiment.

BACKGROUND: Vasospasm frequently accompanies manipulation of small vessels during free flap surgeries and replantations. The purpose of this experimental study was to evaluate the effect of magnesium sulphate on vasospasm provoked by surgical manipulation (axial tension) on the flap pedicle. This kind of surgical manipulation of the vessel cannot be studied in a clinical environment without putting flap viability into risk. MATERIAL AND METHODS: Forty male Wistar rats weighing around 300 g each were classified in two experimental groups (n=20 in each). In the treatment group (group A) Magnesium Sulphuricum 10% (Biotika, Czech Republic) was applied; the second group (group B) served as a control. The vasopasm was provoked by pulling the pedicle of the right groin flap of the rat. The peripheral blood perfusion of the flap was continuously measured using laser-Doppler recording. In the study group, magnesium sulphate was applied topically on the flap pedicle to relieve vasospasm, and duration of the vasospasm was compared to the control group. RESULTS: A statistically significant difference (p=0.01) between the groups was found. The duration of vasospasm was significantly shorter in the treatment group A. CONCLUSIONS: We conclude that in an experimental environment magnesium sulphate is effective in relieving surgically provoked vasospasm of the flap pedicle. This finding is in accordance with our clinical observations.

The effect of blood around a flap pedicle on flap perfusion in an experimental rodent model.

BACKGROUND: The vasospasm has been studied to a considerable extent in the neurosurgical literature. Little experimental and basic scientific literature about vasospasm of flap pedicle is available in the field of reconstructive microsurgery. The purpose of the study was to investigate the effect of presence of blood around the pedicle on a flap perfusion. MATERIAL AND METHODS: Blood flow through a right groin flap was continuously measured using Laser Doppler flowmetry on 40 male Wistar rats. A segment of the flap's pedicle was surgically cleared of adventitia and bathed in blood. The blood used was either collected from the tail of the rat (group A) or from the bleeding branch of the pedicle itself (group B). The differences between the signal amplitudes before and after exposure of the pedicle to blood were recorded. RESULTS: The presence of blood around the pedicle resulted in a significant decrease in perfusion of the flap in both groups. However, no significant differences in the duration of impaired blood flow between the groups were observed. CONCLUSIONS: In conclusion, the presence of blood around the vascular pedicle may cause a significant decrease in the perfusion of a flap, while the origin of the blood does not appear to be an important factor.

Nuclear receptors gene polymorphisms and risk of restenosis and clinical events following coronary stenting.

INTRODUCTION: Hereditary factors connected with inflammation and fibroproliferation may play important role in restenotic process after coronary stenting. Peroxisome proliferator-activated receptors (PPAR) and retinoic X receptors (RXR) regulate the transcription of crucial genes involved in the glucose and lipid metabolism, inflammation and cell differentiation. METHODS: In our angiographic and clinical study we assessed the association of gene polymorphisms of L162V for PPAR-alpha, C161T for PPAR-gamma and A(39526)AA for RXR-alpha with the risk of restenosis and cardiac events after coronary stenting. Primary endpoint was diameter stenosis > or = 50% at follow-up angiography. Secondary endpoints were death, myocardial infarction and/or target lesion revascularisation at 12 months, and clinical restenosis. The results were adjusted for known predictors of restenosis. The genotypes were analysed by polymerase chains reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. RESULTS: Control angiography was performed in 477 of 565 patients (84.4%) with following restenosis rates in genotype subgroups: CC 29.0% vs GC/GG 22.6% (p = 0.33) in L162V, CC 29.9% vs TC/TT 24.6% (p = 0.24) in C161T and A/A 26.9% vs A/AA + AA/AA 35.0% (p = 0.14) in A(39526)AA polymorphisms. The T allele ofC161T polymorphism was associated with lower frequency of clinical restenosis (p = 0.015). CONCLUSION: We could not find an association of L162V PPAR-alpha, C161T PPAR-gamma and A(39526)AA RXR-alpha gene polymorphisms with angiographic in-stent restenosis or major cardiac events. However, we found the relationship between C161T PPAR-gamma polymorphism and clinical restenosis deserving further study.

Genetics of humoral and cytokine activation in heart failure and its importance for risk stratification of patients.

The study objective is to prove an association among plasma concentration of big endothelin and endothelin-1, other clinical parameters and two frequent polymorphisms - G8002A and -3A/-4A - in the endothelin-1 (EDN-1) coding gene (6p21-23), and among plasma concentration of TNF alpha and gene polymorphisms TNF alpha -308 A/G, -238 A/G, TNF beta Ncol and 3'TACE (tumour necrosis factor alpha converting enzyme) in patients with chronic heart failure (CHF). The second objective is to find an association between polymorphisms G8002A and -3A/4A EDN-1 with diabetes mellitus (DM), peripheral artery disease (PAD) and myocardial infarction (MI) in patients with chronic heart failure (CHF). The study population included 266 patients with symptomatic CHF and proven dysfunction of the left ventricle (LV). Genotyping and plasma concentrations of humoral substances were examined in 224 patients with ejection fraction (EF) below 40%. No associations between plasma concentrations of endothelin-1 and big endothelin and polymorphisms G8002A (p=0.87, p=0.81) and -3A/-4A (p=0.871, p=0.749) in the gene coding endothelin-1 were found. No associations were observed between plasma concentration of TNF alpha and genotypes in four polymorphisms in TNF alpha, beta and TACE genes. A significant correlation was seen between plasma concentration of big endothelin and pulmonary congestion. Patients with ischemic heart disease (IHD) and previous MI showed a difference in the distribution of genotype G8002A for endothelin-1: allele G 0.718 and A 0.282 vs those without MI: allele G 0.882 and A 0.118, (p<0.05). Patients with IHD and DM had allele G in 0.67 and A 0.33, while those without DM had allele G in 0.790 and A in 0.209 (p<0.03). Patients with IHD and concomitant PAD had allele G in 0.718 and A in 0.282 vs those without PAD allele G in 0.882 and A in 0.118 (p<0.0004). Patients with dilative cardiomyopathy (DCMP) showed no differences in genotype G8002A and presence of DM or PAD. It might be speculated that in the case of endothelin-1 and TNF alpha in CHF the genetic determination is not important, and plasma concentrations are influenced more by the disease severity. Ischemics with previous MI, concomitant DM or PAD showed more frequently allele A and less often allele G than those without these diseases. A genotype with allele A is associated with higher risk of concomitant diseases.

[Definition of 24 hour ambulatory blood pressure values corresponding to office blood pressure values of 130/80 mm Hg]. / Stanovení hodnot 24hodinového ambulantního monitorování krevního tlaku odpovídajících kazuálnímu tlaku 130/80 mm Hg.

BACKGROUND: Ambulatory blood pressure monitoring (ABPM) provides a profile of blood pressure (BP) away from the medical environment and has been shown to be a stronger predictor of cardiovascular morbidity and mortality than office BP measurement. There are known the normal BP values for ABPM in general population with office BP value 140/90 mm Hg, but don't are known normal values for ABPM of patients with high risk hypertension which needs to have office BP below 130/80 mm Hg. AIM OF STUDY: Definition of normal BP value of ABPM in patients with office BP130 and/or 80 mm Hg. METHODS: BP measurement in 241 healthy subjects by ABPM and mercury sphygmomanometer according to European Hypertension Society criteria. Subject selection with following criteria: mean office systolic blood pressure 128-132 mm Hg or diastolic blood pressure 78-82 mm Hg. Exclusion ABPM curves with white-coat hypertension and masked hypertension. All office and ABPM inclusion criteria fulfill 37 subjects for systolic blood pressure, mean age 44 years and 48 subjects for diastolic blood pressure, mean age 45 years. RESULTS: Mean office systolic BP 129.9 +/- 1.6 mm Hg, diastolic BP 80.2 +/- 1.5 mm Hg. Mean 24hour systolic BP 119.1 +/- 12.3 (95% CI, 119.0-119.3) mm Hg, diastolic BP 71.4 +/- 10.2 (95% CI, 71.3-71.5) mm Hg, day time systolic BP 123.7 +/- 9.0 (95% CI, 123.6-123.8) mm Hg, diastolic BP 75.4 +/- 7.0 (95% CI, 75.3-75.5) mm Hg, night time systolic BP 105.8 +/- 10.4 (95% CI, 105.7-105.9) mm Hg and diastolic BP 59.8 +/- 9.0 (95% CI, 59.7-59.8) mm Hg. CONCLUSION: The normal BP value ofABPM in patients with office BP 130/80 mm Hg is for 24hour BP 119/71 mm Hg, day time BP 124/75 mm Hg and night time BP 106/60 mm Hg.

Modulation of expression of the sigma receptors in the heart of rat and mouse in normal and pathological conditions.

The aim of the present work was to study the effect of various stressors (hypoxia, cold, immobilization) on the gene expression of sigma receptors in the left ventricles of rat heart. We have clearly shown that gene expression of sigma receptors is upregulated by strong stress stimuli, such as immobilization and/or hypoxia. Nevertheless, cold as a milder stressor has no effect on sigma receptor's mRNA levels. Signalling cascade of sigma receptors is dependent on IP(3) receptors, since silencing of both, type 1 and 2 IP(3) receptors resulted in decreased mRNA levels of sigma receptors. Physiological relevance of sigma receptors in the heart is not clear yet. Nevertheless, based on the already published data we can assume that sigma receptors might participate in contractile responses in cardiomyocytes.

[Insertion-deletion polymorphism in the gene for angiotensin-converning enzyme (I/D ACE) in pregnant women with gestational diabetes]. / Inzercne-delecní polymorfismus v genu pro angiotensin-konvertující enzym (I/D ACE) u tehotných s gestacním diabetem.

AIM OF THE STUDY: The aim of the study was to investigate possible associations of the Angiotensin-converting enzyme insertion/deletion (I/D ACE) polymorphism with gestational diabetes mellitus occurrence. METHODS: Number of 53 healthy pregnant women (controls) and 48 women with gestational diabetes mellitus were included in the study. The woman patients were hospitalised in the Clinic of Obstetrics and Gynaecology, Masaryk University Affiliated hospital Brno during the period 10/2004 - 10/2005. In all cases there was the spontaneous one baby pregnancy. The procedure was obtaining the peripheral blood samples from women of those two groups and isolation of their DNA using standard technique with the use of proteinase K. I/D ACE genotype of each person was determined using allele specific primers. RESULTS: We did not prove significant association neither of the genotype distribution (P(g)) P(g) = 0.115 nor allele frequency (P(a)) P(a) = 0.873 between controls and women with gestational diabetes mellitus. The significant differences of genotype distributions (P(g) = 0.03) were observed in women with two and more labours in anamnesis. Borderline significant differences of genotype distributions (P(g) = 0.08) were found in women with one and more abortions in anamnesis. CONCLUSIONS: According to our results the variability in ACE gene can be taken as factor contributing to manifestation of gestational diabetes mellitus. According to results of our study I/D ACE polymorphism can't be taken as genetic marker of gestational diabetes mellitus.

[Association of polymorphic variants in endothelin-1 (EDN1) genes with the therapy of patients with cutaneous T-cell lymphomas]. / Asociace variant polymorfismu v genu pro endotelin-1 (EDN1) s terapií u pacientu s kozními T lymfomy.

BACKGROUND: The cutaneous T-cell lymphomas (CTCL) are diseases characterised by cutaneous infiltrates of malignant, clonally expanded T-cells. Because individual genetic determination of angiogenetic and antioxidant properties of blood vessels could take part in responsibility to phototherapy in CTCL patients, the association of two frequent polymorphisms in endothelin-1 gene with phototherapy was tested. METHODS AND RESULTS: 77 patients with CTCL, diagnosed and treated at the First Dermatological Clinic of St. Ann's Faculty Hospital Bmo (46 men and 31 women, median age 62, range 28-82 years) were included in the study. Diagnosis of CTCL according to the clinical picture was verified histologically. The genotype distributions and allelic frequencies between CTCL with phototherapy and those without phototherapy were compared. The 4A4A variant of -3A/-4A EDN1 is more frequent in patients treated with phototherapy (8/30 vs. 1/38, OR=10.13; P=0.01). The GA and AA genotypes of G8002A EDN1 polymorphism are more frequent in CTCL patients treated with phototherapy compared to those without it (15/23 vs. 7/32, OR=2.98; P=0.03). CONCLUSIONS: Some polymorphic variants in EDN1 genes, a homozygote -4A-4A in -3A/-4A EDN1 and genotypes GA and GG in G8002A EDN1) seem to carry an advantage for phototherapy effectiveness in patients with CTCL.

[Pharmacogenetics of chronic heart failure--beta blockers]. / Príspevek k farmakogenetice chronického srdecního selhání--betablokátory.

BACKGROUND: Activation of the renin-angiotensin (RAS) cascade and sympathetic nervous systems adversely affect heart failure progression. ACE deletion allele (ACE D) of insertion/deletion polymorphism in the gene coding for angiotensin-1 converting enzyme is associated with increased renin-angiotensin activation. The aim of the study was to test pharmacogenetic associations of I/D ACE genotype with beta blockers therapy in patients with chronic heart failure. METHODS AND RESULTS: A total of 241 patients were included in the study, 63% with betablocker therapy and 37% without it. Using polymerase chain reaction (PCR) method, I/D genotype was detected in 2% agarose electrophoretic gel in UV light. Patients with chronic heart failure and with the II genotype of polymorphism I/D ACE were younger, with more frequent administration of betablockers and diuretics, with less regular administration of aspirin and with lower glycemia and plasma TNFalpha level. A significant difference in genotype distribution and allele frequency between patients with recommended dose and patients without betablockers therapy was proved, when a decrease of the D allele in patients with betablockers had been observed. Contemporary evaluating of AC inhibitor and betablocker therapy, a decrease of ID+DD genotypes in patients with lower than 50% recommended dose compared with the others was found. CONCLUSIONS: In this study, we proved statistically significant interactions between genotypes in I/D ACE polymorphism, betablocker administration, its dosing and pharmacogenetic interaction with ACE inhibitors in patients with chronic heart failure.

[Polymorphism of gene promotor region for MMP-2 in rheumatoid arthritis]. / Polymorfizmus v promotorové oblasti genu pro MMP-2 u revmatoidní artritidy.

INTRODUCTION: Matrix metalloproteinase (MMP) belonging to family of zinc-dependent endopeptidases participates in remodelling of extracellular matrix in many physiological and pathological processes including rheumatoid arthritis (RA). Rheumatoid arthritis is a chronic autoimmune inflammatory multi-systemic disease characterized, among others, by degradation of hyaline articular cartilage and escalated angiogenesis. As a matter of fact, these processes may by influenced by MMP. On the other hand, MMP can suppress inflammation by degrading biologically active molecules like cytokines, chemokines or growth factor receptors. Increased levels of MMP-2 (gelatinase A) are observed in serum and synovial fluid of patients with RA. Gene polymorphism for MMP-2 can affect susceptibility to development and/or severity of RA. METHOD: The aim of the study was to prove possible association of polymorphisms in gene promotor region for MMP-2 (-1575 G/A, -1306 C/T, -790 T/G, -735 C/T) with RA. We worked with 101 patients with RA who met reviewed diagnostic criteria of ACR (1987) for RA, and suffer from RA for at least 2 years. Control group consisted of 101 healthy volunteers of similar age and gender distribution. RESULTS: RA patients and control group did not differ in genotype distributions or frequencies of alleles of polymorphisms -1575A/G, -1306C/T and -735 C/T. Significant difference was observed between RA patients and control group in allelic frequencies of polymorphism -790 T/G MMP-2 (T allele -0.70 vs. 0.66, Pa = 0.013). Also, a tendency of GG genotype growth was noted in RA patients (Pg = 0.053). Significant difference in allelic frequencies was also observed between men with RA and men from control group (T allele -0.80 vs. 0.61, Pa = 0.025). Haplotype of GCGC polymorphisms -1575 G/A, -1306 C/T, 790 T/G, -735 C/T was more frequent in RA patients (Pcorr = 0.016; OR = 0.09; confidence interval 0.00-0.65), whereas GCTC haplotype was noted more frequently in control group (Pcorr = 0.017; OR = 1.8; confidence interval 1.17-2.70). CONCLUSION: The results indicate the association between polymorphisms in gene promotor region for MMP-2 and susceptibility to development of RA.