UNLABELLED: Several mutations in this gene for the α subunit of the cardiac sodium channel have been identified in a heterogeneous subset of cardiac rhythm syndromes, including Brugada syndrome, progressive cardiac conduction defect, sick sinus node syndrome, atrial fibrillation and dilated cardiomyopathy. The aim of our study was to associate some SCN5A polymorphic variants directly with confirmed coronary stenoses in patients with non-LQTS ventricular fibrillation/flutter treated by an implantable cardioverter defibrillator. MATERIALS AND METHODS: A group of 32 unrelated individuals, aged 63 ± 12 years, was included in the study. All the patients were examined, diagnosed and treated with an implantable cardioverter defibrillator at the Department of Internal Cardiology Medicine, Faculty Hospital Brno. The control group included 87 persons of similar age without afflicted coronary circulation, which was confirmed coronagraphically. Genomic DNA was extracted from samples of peripheral blood according to the standard protocol. Two SCN5A polymorphisms-IVS9-3C/A (rs41312433) and A1673G (rs1805124, H558R)-were examined in association with coronary artery stenosis in the patients. RESULTS: In the case-control study, no significant differences in genotype distribution/allelic frequencies were observed for IVS9-3c>a and A1673G gene polymorphisms between patients with severe arrhythmias and healthy persons. The distribution of SCN5A double genotypes was not significantly different among different types of arrhythmias according to their ejection fraction in arrhythmic patients (p = 0.396). The ventricular arrhythmias with an ejection fraction below 40% were found to be 10.67 times more frequent in patients with multiple coronary stenosis with clinically valid sensitivity, specificity and power tests. In the genotype-phenotype study, we observed a significant association of both SCN5A polymorphisms with the stenosis of coronary vessels in the patients with severe arrhythmia. The double genotype of polymorphisms IVS9-3C/A together with A1673G (CCAA) as well as their simple genotypes were associated with significant multiple stenosis of coronary arteries (MVS) with high sensitivity and specificity (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.70; specificity 0.682; power test 0.359) Moreover, when a concrete stenotic coronary artery was associated with SCN5A genotypes, the CCAA double genotype was observed to be five times more frequent in patients with significant stenosis in the right coronary artery (RCA) compared to those without affliction of this coronary artery (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.682; specificity 0.700; power test 0.359). The CCAA genotype was also more frequent in patients without RCA affliction with MVS (p = 0.008); in patients with ACD affliction but without MVS (p = 0.008); and in patients with both ACD affliction and MVS compared to those without ACD affliction and MVS (p = 0.005). CONCLUSIONS: Our study presents a highly sensitive and specific association of two polymorphisms in SCN5A with significant coronary artery stenoses in patients with potentially fatal ventricular arrhythmias. At the same time, these polymorphisms were not associated with arrhythmias themselves. Thus, SCN5A gene polymorphic variants may form a part of germ cell gene predisposition to ischemia.

• MeSH
• fenotyp MeSH
• fibrilace síní * genetika   MeSH
• koronární cévy * MeSH
• lidé MeSH
• napěťově řízený sodíkový kanál, typ 5 genetika   MeSH
• stenóza MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

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.

• MeSH
• angiotensin konvertující enzym genetika   MeSH
• angiotensin-konvertující enzym 2 MeSH
• Betacoronavirus fyziologie   MeSH
• COVID-19 MeSH
• genetická predispozice k nemoci MeSH
• interakce hostitele a patogenu genetika   MeSH
• koronavirové infekce genetika   MeSH
• lidé MeSH
• pandemie MeSH
• SARS-CoV-2 MeSH
• virová pneumonie genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

Matrix metalloproteinases (MMPs) as well as their inhibitors (TIMPs) play a crucial role in controlling extracellular matrix turnover and have recently been associated with atherosclerosis, myocardial and vascular injury. Moreover, the genetic variability of MMP genes has been suggested to play an important role in vascular remodeling and age-related arterial stiffening. This study aims to describe associations of 14 selected polymorphisms in genes for MMPs and TIMPs with selected cardiovascular parameters (including central pulse pressure), clinical conditions and drug treatment profiles in 411 stable ischemic patients with preserved systolic function of the left ventricle. The genotyping of 14 single-nucleotide polymorphisms in 8 genes was carried out either using 5´ exonuclease (TaqMan®) reagents or by restriction analysis. Numerous associations of the investigated polymorphisms with systolic and diastolic blood pressure, maximum left ventricular end diastolic pressure and ejection fraction were observed. While some of the observed effects were found to be age-dependent, associations with clinical conditions (hypertension, diabetes mellitus, angina pectoris) were only observed in women and associations with four groups of drugs (statins, nitrates, calcium channel blockers, anti-aggregation drugs) were only observed in men. The results of this study indicate that the genetic variability of MMPs and TIMPs is an important factor which influences cardiovascular functions and may have important consequences for individual therapy customization in the future.

• MeSH
• genetická variace MeSH
• ischemická choroba srdeční farmakoterapie   genetika   patofyziologie   MeSH
• kardiovaskulární látky terapeutické užití   MeSH
• krevní tlak * MeSH
• lidé MeSH
• matrixové metaloproteinasy genetika   MeSH
• tkáňové inhibitory metaloproteinas genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND AIM: The objective of this research was to determine whether invasively measured central pulse pressure (PP) in patients indicated for coronarography is associated with two common polymorphisms in the ACE2 region (rs4646156 and rs4646174). METHODS: A total of 307 patients were enrolled in the study. The genotyping of both SNPs from peripheral blood samples was carried out using 5'exonuclease (Taqman®) chemistry on the ABI Prism® 7000 system (Applied Biosystems, Foster City, CA, USA). RESULTS: In both polymorphisms, the associations with central PP were found to be highly significant when all five possible genotypes in the population had been compared (p = 0.0001). In men, there was a higher incidence of previous myocardial infarction in G0 genotype carriers of rs54646174 (OR ratio = 7; p = 0.005). The AA genotype of rs4646156 had a 7.81× higher risk of severe angina pectoris in women (OR = 7.81, p = 0.05). A significant difference in allelic frequency of ACE2rs4646174 was found between women with and without significant stenoses of the circumflex branch of the left coronary artery. CONCLUSION: More research into the role of ACE2 genetic variability in PP regulations is necessary for more detailed physiological and pathophysiological comprehension of PP regulation.

• MeSH
• angiotensin konvertující enzym genetika   MeSH
• demografie MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• kardiovaskulární nemoci enzymologie   genetika   patofyziologie   radiografie   MeSH
• koronární angiografie * MeSH
• krevní tlak * MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• pulz MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The aim of this study was to investigate possible associations of the five DNA polymorphic genotypes in the HLA region (transporter associated with antigen processing [TAP1; TAP1 333 a/b, TAP1 637 c/d], the HLA-DRB1*1501-rs3135388, tumor necrosis factor [TNF]α [-238 G/A] and NcoI TNFβ) with characteristics of family history in patients with psoriasis vulgaris. MATERIALS AND METHODS: A total of 201 Czech patients with psoriasis were enrolled in the study. The patients were genotyped for the five common polymorphisms in TAP1, TNFα, and TNFβ genes (6p21.3) using the polymerase chain reaction-restriction fragment length polymorphism-based methodology. RESULTS: We observed significantly higher prevalence of Ile333Ile TAP1 allele in patients whose first-degree relatives had a positive family history of psoriasis (Pa = 0.04). No differences related to family history of psoriasis were observed in HLA-DRB1*1501 polymorphism. As for the TNFα (-238 G/A) polymorphism, a significant increase of the GG genotype was observed in patients, especially men with second- and third-degree relatives with psoriasis (Pg = 0.008). Similarly, the B2B2 genotype of NcoI TNFβ polymorphism was more frequent in psoriatic patients, especially women, whose second- and third-degree relatives had psoriasis (Pg = 0.004). Finally, the haplotype analysis of all five polymorphisms revealed that the frequency of haplotype bcCB1A was different between not only men and women with psoriasis (P = 0.007) but also between men and women without a family history of psoriasis (P = 0.007). CONCLUSIONS: Haplotype association of HLA gene polymorphisms with genealogy aspects of psoriasis facilitates a better understanding of etiopathogenetic aspects of the diseases.

• MeSH
• ABC transportéry genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci epidemiologie   genetika   MeSH
• haplotypy MeSH
• HLA-DRB1 řetězec genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfotoxin-alfa genetika   MeSH
• polymorfismus délky restrikčních fragmentů MeSH
• polymorfismus genetický MeSH
• psoriáza epidemiologie   genetika   MeSH
• rizikové faktory MeSH
• senioři MeSH
• TNF-alfa genetika   MeSH
• zdraví rodiny MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Projekt naplňuje cíle "Resortního programu výzkumu a vývoje II MZ na léta 2009-2011": v oblasti vypracování nových dignostických postupů vycházejících z genetické identifikace chorob, respektive z genetické identifikace predispozice k vysokému pulsnímu tlaku a tím hledání nových postupů v prevenci koronárních a cerebrovaskulárních chorob. Výsledky projektu mohou vést k hledání nových cest k ovlivnění hodnoty pulsního tlaku, který je významným prediktorem kardiovaskulární mortality. Vysoký pulsní tlak byse tak mohl stát jedním z terapeutických cílů. Předpokládaný okruh příjemců řešení je odborná veřejnost v oblasti kardiologie, fyziologie a molekulární biologie, klinické farmakologie a farmakogenetiky.; The project completes aims of "Resort Programme of Research and Development II of Ministry of Health for years 2009-2011": at the area of finding of new diagnostic genetic markers of diseases or of identification of genetic predisposition markers for a high pulse pressure. This is the way to find new approaches in coronary and cerebrovascular diseases prevention. New ways how to influence the pulse pressure level will be useful because its level is a serious predictor of cardiovascular mortality. The high pulse pressure could become one of the new therapeutic target. The results of the project could accost a large professional public in cardiology, pathophysiology, molecular biology, clinical pharmacology and pharmacogenetics.

• MeSH
• celogenomová asociační studie MeSH
• inhibitory ACE MeSH
• inhibitory matrixových metaloproteinas MeSH
• kardiovaskulární nemoci MeSH
• krevní tlak MeSH
• matrixové metaloproteinasy MeSH
• polymorfismus genetický MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• kardiologie
• angiologie
• biologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

Atherosclerosis as a main etiopathogenetic source for coronary artery disease (CAD) development is intimately related to dynamic changes in the extracellular matrix (ECM). Elevated levels of MMP-13 have been observed in human atherosclerotic plaques which could also involve variability in MMP-13 gene. The aim of the study was to associate rs640198 polymorphism with CAD and/or with its severity. The study comprised 1071 consecutive patients with suspected or known coronary artery disease (CAD), confirmed by coronary angiography. Genotyping for the rs640198 polymorphism in MMP-13 gene was performed using Taqman® assay. The TT and TG genotypes of rs640198 polymorphism in MMP-13 gene confer the significantly increased risk of triple vessel disease compared to patients without atherosclerotic lesions in coronary arteries (odds ratio=1.64, Pcorr=0.05). Furthermore, an increased risk of having 5 and more stenoses (odds ratio=1.90, Pcorr=0.004) was observed in TT and TG carriers (sensitivity of 0.613 and a specificity of 0.544; power of the test is 0.87). T allele of MMP-13 intron polymorphism rs640198 is associated with the severity of coronary artery disease, represented by the number of affected arteries as well as by the number of stenoses confirmed by coronarography.

• MeSH
• dospělí MeSH
• genetické testování MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 13 genetika   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoci koronárních tepen genetika   radiografie   MeSH
• polymorfismus genetický MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH