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. The aim of the study was to test an association among haplotypes of four single nucleotide MMP-2 promoter polymorphisms and the angiographically confirmed coronary triple-vessel disease (TVD). Incidence of haplotypes of four MMP-2 promoter polymorphisms (-1575G/A, -1306C/T, -790T/G and -735C/T) determined by PCR reactions with restriction analyses in 187 patients with coronary TVD (153 men, 34 women, age median 65 years) was compared to 196 control subjects without clinical signs of coronary heart disease (131 men and 65 women, age median 60 years). The incidence of two similar haplotypes was found to be different between patients and healthy subjects. The haplotype GCTC was more frequent in the TVD patients (P=0.01) though the haplotype GCGC was identified only in healthy subjects (P=0.001). Interestingly, the GCTC is the most frequent polymorphic haplotype composed of four promoter SNPs localized in the MMP-2 gene (53% in healthy subjects vs. 66% in patients with TVD) and the haplotype GCGC is the least frequent polymorphic one (4.4% in healthy subjects vs. 0% in patients with TVD). Two different MMP-2 promoter haplotypes differing only in -790T/G allele are significantly more or less frequent in coronary TVD compared to non-ischemic persons. Thus, the -790T/G MMP-2 genotype might be used as a genetic marker representing MMP-2 promoter variability for the TVD with odds ratio for TT and TG genotypes 2.59, 95% confidential interval 1.21-5.55, P=0.009. The analysis of promoter MMP-2 gene variability could help us to understand individual susceptibility to MMP inhibitor treatment of the coronary artery disease.

• MeSH
• adenin MeSH
• alely MeSH
• cytosin MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická variace MeSH
• genotyp MeSH
• guanin MeSH
• haplotypy * MeSH
• jednonukleotidový polymorfismus * MeSH
• koronární nemoc genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• matrixová metaloproteinasa 2 genetika   MeSH
• promotorové oblasti (genetika) genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• thymin 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
• Názvy látek
• adenin MeSH
• cytosin MeSH
• guanin MeSH
• matrixová metaloproteinasa 2 MeSH
• thymin MeSH

INTRODUCTION: Periprocedural bleeding related to coronary angiography (CAG) or percutaneous coronary intervention (PCI) is associated with worse prognosis. Determining genetic variations associated with increased bleeding risk may help to identify high-risk patients. AIM: To analyse the association between single nucleotide polymorphisms (SNPs) of crucial haemostatic platelet receptors (GPIa, GPVI, P2Y12) and the risk of periprocedural bleeding complications related to CAG/PCI. MATERIAL AND METHODS: The population consisted of 73 patients with ischaemic heart disease who developed bleeding complications within 30 days after CAG/PCI and 331 patients without bleeding. The frequency of SNPs of GPIa 807C/T, GPVI 13254T/C, P2Y12 32C/T, and P2Y12 H1/H2 haplotype was analysed using polymerase chain reaction (PCR) hybridization methods. RESULTS: The prevalence of variant alleles GPIa 807T, GPVI 13254C, P2Y12 34T, and P2Y12 H2 haplotype in the total study population was 56.7%, 20.3%, 56.2%, and 24.3%, respectively. The presence of variant alleles was not related to increased risk of periprocedural bleeding: GPIa 807C/T (OR = 1.29, 95% CI: 0.75-2.24, p = 0.334), GPVI 12354T/C (OR = 0.82, 95% CI: 0.40-1.64, p = 0.551), P2Y12 34C/T (OR = 0.71, 95% CI: 0.42-1.22, p = 0.189), P2Y12 H1/H2 haplotype (OR = 0.69, 95% CI: 0.35-1.36, p = 0.258). The frequency of the homozygous form of P2Y12 H2 haplotype was higher in the group of patients who developed bleeding (OR = 2.79, 95% CI: 0.51-13.77, p = 0.161). CONCLUSIONS: No significant association of the SNPs of GPIa 807C/T, GPVI 13254T/C, P2Y12 32C/T, and P2Y12 H1/H2 haplotype with increased risk of periprocedural bleeding was found in patients with ischaemic heart disease undergoing CAG/PCI.

• Klíčová slova
• ischaemic heart disease, periprocedural bleeding, platelet receptors, single nucleotide polymorphism,
• Publikační typ
• časopisecké články MeSH

• MeSH
• DNA analýza   MeSH
• geny MHC třídy I * MeSH
• H-2 antigeny genetika   MeSH
• haplotypy MeSH
• hybridizace nukleových kyselin MeSH
• klonování DNA MeSH
• myši MeSH
• transfekce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA MeSH
• H-2 antigeny MeSH

PRDM9-mediated reproductive isolation was first described in the progeny of Mus musculus musculus (MUS) PWD/Ph and Mus musculus domesticus (DOM) C57BL/6J inbred strains. These male F1 hybrids fail to complete chromosome synapsis and arrest meiosis at prophase I, due to incompatibilities between the Prdm9 gene and hybrid sterility locus Hstx2. We identified 14 alleles of Prdm9 in exon 12, encoding the DNA-binding domain of the PRDM9 protein in outcrossed wild mouse populations from Europe, Asia, and the Middle East, 8 of which are novel. The same allele was found in all mice bearing introgressed t-haplotypes encompassing Prdm9. We asked whether 7 novel Prdm9 alleles in MUS populations and the t-haplotype allele in 1 MUS and 3 DOM populations induce Prdm9-mediated reproductive isolation. The results show that only combinations of the dom2 allele of DOM origin and the MUS msc1 allele ensure complete infertility of intersubspecific hybrids in outcrossed wild populations and inbred mouse strains examined so far. The results further indicate that MUS mice may share the erasure of PRDM9msc1 binding motifs in populations with different Prdm9 alleles, which implies that erased PRDM9 binding motifs may be uncoupled from their corresponding Prdm9 alleles at the population level. Our data corroborate the model of Prdm9-mediated hybrid sterility beyond inbred strains of mice and suggest that sterility alleles of Prdm9 may be rare.

• Klíčová slova
• Hstx2, Mus musculus, Prdm9, t-haplotype, asynapsis, fertility, reproductive isolation,
• MeSH
• exony MeSH
• fenotyp MeSH
• histonlysin-N-methyltransferasa genetika   metabolismus   MeSH
• infertilita * genetika   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• zinek MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• histonlysin-N-methyltransferasa MeSH
• PRDM9 protein, human MeSH Prohlížeč
• prdm9 protein, mouse MeSH Prohlížeč
• zinek MeSH

The male-sterile reciprocal autosomal translocation T(16;17)43H displays a high frequency of adjacent-2 disjunction in meiosis of translocation heterozygotes. One haploid product of this abnormal chromosome segregation leads to viable partial trisomy of chromosome 17 after fertilization. The frequency of trisomics increases in the progeny of T43H/+ females when the wild-type allelic form of T-t complex is substituted for t12, tw32 or t6 recessive lethal haplotypes. Indirect evidence supports the idea that the suppression of crossing-over by t haplotypes is linked with the increase in adjacent-2 disjunction and subsequent Ts43H trisomy. The possible use of Ts43H trisomy for genetic dissection of the T-t complex is briefly discussed.

• MeSH
• chromozomy MeSH
• crossing over (genetika) MeSH
• geny recesivní MeSH
• haploidie MeSH
• inbrední kmeny myší genetika   MeSH
• letální geny MeSH
• myši MeSH
• translokace genetická MeSH
• trizomie MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

MHC class I downregulation is an important mechanism of tumour escape from T cell-mediated immune responses. Approximately 40-90% of human tumours derived from various MHC class I+ tissues were reported to be MHC class I deficient. Decreased or absent MHC class I expression is frequently associated with the invasive and metastatic tumour phenotype. Altered MHC class I antigen expression involves total loss, loss of haplotype, locus downregulation, allelic loss or downregulation, and combinations. Description of partial or complete losses of MHC class I molecules in tumour cells as mechanisms of immune escape often fails to consider an increased susceptibility to NK cell-mediated lysis, which is a direct consequence of such losses. A low MHC class I level favours NK cells as effectors, whereas a high level of MHC class I favours T cells as effectors. The microheterogeneity of MHC class I expression in tumour cell populations, the balance of the MHC-restricted and MHC-unrestricted defence as well as the selective pressure of antigen-specific (CTL) and antigen non-specific (NK) effector mechanisms decide the final outcome of the MHC class I expression in the primary tumour and its metastases as well as the final outcome of the tumour defence reaction. Despite the MHC class I molecule deficiency and the resulting absence of the CD8+ T cell-mediated immunity, the tumour hosts were found to be capable of being immunized against MHC class I- tumours. The purpose of this review is to discuss the positive results of MHC class I- tumour treatment obtained with immunomodulatory cytokines and tumour vaccines, as well as the prospects and limitations of such therapy.

• MeSH
• alely MeSH
• buňky NK cytologie   MeSH
• CD8-pozitivní T-lymfocyty metabolismus   MeSH
• down regulace * MeSH
• fenotyp MeSH
• haplotypy MeSH
• histokompatibilita - antigeny třídy I biosyntéza   imunologie   MeSH
• imunoterapie metody   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory imunologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• histokompatibilita - antigeny třídy I MeSH

BACKGROUND: The CTLA4 (cytotoxic T-lymphocyte antigen 4) gene is associated with several immunopathologic diseases and because of its important immuno-regulatory role it may be considered also a plausible candidate for a genetic association with inflammatory bowel diseases. Previously published studies found no association of CTLA4 with Crohn's disease itself, but some indicated an association with its subphenotypes. The aim of this study was to assess the association in the Czech population, using a set of markers shown to associate with other diseases. METHODS: Six polymorphisms within the CTLA4 region were investigated in 333 patients with Crohn's disease and 482 unrelated healthy controls, all Caucasians of Czech origin. The genotypes of the SNPs were determined using the TaqMan SNP genotyping assays. Haplotypes were reconstructed using an expectation-maximization algorithm, and their association with the condition was assessed using log-linear modeling. Then, potential interactions were tested between the CTLA4 variants and other genetic factors known to confer the disease susceptibility. RESULTS: No crude associations with Crohn's disease were found for the tested CTLA4 variants under the log-additive or dominant models. However, when stratified for the genetic risk conferred by the variants in the NOD2 (the p.Leu1007fsX1008, rs5743293) or the IL23R (p.R381Q, rs11209026), a significant negative association emerged for the minor alleles of CTLA4 CT60 (rs3087243), JO31 (rs11571302), JO27-1 (rs11571297) polymorphisms. This negative association with CTLA4 was apparent only in the strata defined by presence minor alleles at the NOD2 rs5743293 (here the CTLA4 CT60 A coffered an OR = 0.43, 95%CI 0.19 - 0.95 for the presence of CT60 A), or IL23R rs11209026 (here the OR for presence of CT60 A was 0.23, 95%CI 0.07 - 0.71). We observed this effect also for the haplotype consisting of minor alleles of the three tightly linked CTLA4 markers. Furthermore, this haplotype was associated with the younger age at diagnosis (OR 1.52, 95%CI 1.09 - 2.11, p = 0.014). CONCLUSIONS: A protective effect of a CTLA4 haplotype was unmasked after stratification for the risk variants in the NOD2 and IL23R genes, and may point towards the biological relevance of the molecule in the pathogenesis of the disease.

• MeSH
• alely MeSH
• antigen CTLA-4 MeSH
• běloši genetika   MeSH
• CD antigeny MeSH
• Crohnova nemoc epidemiologie   genetika   MeSH
• cytotoxické T-lymfocyty MeSH
• genotyp MeSH
• haplotypy MeSH
• idiopatické střevní záněty genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigen CTLA-4 MeSH
• CD antigeny MeSH
• CTLA4 protein, human MeSH Prohlížeč

Despite extensive data demonstrating that immature retroviral particle assembly can take place either at the plasma membrane or at a distinct location within the cytoplasm, targeting of viral precursor proteins to either assembly site still remains poorly understood. Biochemical data presented here suggest that Tctex-1, a light chain of the molecular motor dynein, is involved in the intracellular targeting of Mason-Pfizer monkey virus (M-PMV) polyproteins to the cytoplasmic assembly site. Comparison of the three-dimensional structures of M-PMV wild-type matrix protein (wt MA) with a single amino acid mutant (R55F), which redirects assembly from a cytoplasmic site to the plasma membrane, revealed different mutual orientations of their C- and N-terminal domains. This conformational change buries a putative intracellular targeting motif located between both domains in the hydrophobic pocket of the MA molecule, thereby preventing the interaction with cellular transport mechanisms.

• MeSH
• biologické modely MeSH
• biologický transport MeSH
• buněčná membrána metabolismus   virologie   MeSH
• Cercopithecus aethiops MeSH
• COS buňky MeSH
• cytoplazma metabolismus   MeSH
• dyneiny metabolismus   MeSH
• fenotyp MeSH
• genomová oblast t-komplexu MeSH
• jaderné proteiny chemie   metabolismus   fyziologie   MeSH
• lidé MeSH
• Masonův-Pfizerův opičí virus metabolismus   MeSH
• mutace MeSH
• proteiny asociované s mikrotubuly chemie   metabolismus   fyziologie   MeSH
• Retroviridae metabolismus   MeSH
• terciární struktura proteinů MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dyneiny MeSH
• jaderné proteiny MeSH
• proteiny asociované s mikrotubuly MeSH

Extensive linkage disequilibrium among classical laboratory strains represents an obstacle in the high-resolution haplotype mapping of mouse quantitative trait loci (QTL). To determine the potential of wild-derived mouse strains for fine QTL mapping, we constructed a haplotype map of a 250-kb region of the t-complex on chromosome 17 containing the Hybrid sterility 1 (Hst1) gene. We resequenced 33 loci from up to 80 chromosomes of five mouse (sub)species. Trans-species single-nucleotide polymorphisms (SNPs) were rare between Mus m. musculus (Mmmu) and Mus m. domesticus (Mmd). The haplotypes in Mmmu and Mmd differed and therefore strains from these subspecies should not be combined for haplotype-associated mapping. The haplotypes of t-chromosomes differed from all non-t Mmmu and Mmd haplotypes. Half of the SNPs and SN indels but only one of seven longer rearrangements found in classical laboratory strains were useful for haplotype mapping in the wild-derived M. m. domesticus. The largest Mmd haplotype block contained three genes of a highly conserved synteny. The lengths of the haplotype blocks deduced from 36 domesticus chromosomes were in tens of kilobases, suggesting that the wild-derived Mmd strains are suitable for fine interval-specific mapping.

• MeSH
• druhová specificita MeSH
• fylogeneze MeSH
• genová přestavba MeSH
• haplotypy * MeSH
• lidé MeSH
• lidské chromozomy, pár 6 genetika   MeSH
• myši genetika   MeSH
• pilotní projekty MeSH
• savčí chromozomy genetika   MeSH
• sekvenční analýza DNA MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši genetika   MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Gastroesophageal reflux (GERD) is a one of the major public health problem that can lead to reflux esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). The aim of our study was to determine the impact of IL-1 gene polymorphisms on the development of GERD, RE and BE. METHODS: Three hundred and thirty-three Czech patients with gastroesophageal reflux and 165 healthy controls were included in this case-control study. Four polymorphisms in the genes of the IL-1 cluster [IL-1A(-889C/T), IL-1B(-511C/T), IL-1B(+3953C/T), and IL-1RN(VNTR)] were analyzed. RESULTS: Significant differences were found in IL-1RN 1/2 genotype between patients with GERD/RE and controls and in IL-1B+3953 T allele between patients with BE and healthy subjects. In addition, complex analysis revealed differences in IL-1 haplotype frequencies between the groups. Specifically, the haplotype TCCL was significantly more frequent (p = 0.016) in GERD patients than in controls and the haplotype CCCL more frequent (p = 0.008) in RE patients than in controls. However, in patients with BE, frequency of haplotype TCTL was lower (p = 0.05) and haplotypes CTCL and TCCL were higher (p = 0.03 and p = 0.02) in comparison with the controls. CONCLUSIONS: Our results suggest that IL-1 haplotypes may be associated with susceptibility to GERD, RE and BE.

• Klíčová slova
• BE, Barrett’s esophagus, CI, DNA, DU, EAC, EC, EE, GAC, GERD, GIQLI, GU, HWE, Hardy–Weinberg equilibrium, IL-1, LD, LES, NERD, OR, PCR, RE, RFLP, SNP, VNTR, adenocarcinoma of the esophagus, confidence intervals, deoxyribonucleic acid, duodenal ulcer, erosive esophagitis, esophageal cancer, gastric adenocarcinoma, gastric ulcer, gastroesophageal reflux disease, gastrointestinal quality of life index, interleukin-1, linkage disequilibrium, lower esophageal sphincter, non-erosive reflux disease, odds ratio, polymerase chain reaction, reflux esophagitis, restriction fragment length polymorphism, single nucleotide polymorphism, variable number tandem repeat,
• MeSH
• Barrettův syndrom genetika   imunologie   MeSH
• dospělí MeSH
• frekvence genu MeSH
• gastroezofageální reflux genetika   imunologie   MeSH
• genetické asociační studie MeSH
• genotyp MeSH
• haplotypy MeSH
• interleukin-1 genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• multigenová rodina imunologie   MeSH
• studie případů a kontrol MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• interleukin-1 MeSH