Cíl: Stanovení alelové frekvence polymorfizmu p.Val66Met (rs6265) v genu pro mozkový neurotrofní faktor (brain-derived neurotrophic factor; BDNF) v české populaci. Přítomnost polymorfizmu p.Val66Met v genu BDNF je spojována s porušeným intracelulárním transportem a sekrecí BDNF. Změny v expresi a funkci BDNF jsou spojeny s různými onemocněními mozku a představují jeden z mechanizmů odpovědi na stres. Soubor a metodika: Retrospektivně bylo v kontrolní skupině vyšetřeno 317 vzorků DNA jedinců z české populace (173 mužů a 144 žen) ve věku 45–81 let. Polymorfizmus p.Val66Met v genu BDNF byl vyšetřen analýzou křivek tání. Výsledky: Frekvence mutantní alely (A) v kontrolní skupině činila 16,3 %; frekvence standardní alely (G) činila 83,7 %. Závěr: Byla stanovena frekvence polymorfizmu p.Val66Met v genu BDNF, která je srovnatelná s frekvencemi v okolních zemích.
Aim: To determine the allele frequency of the p.Val66Met (rs6265) polymorphism in BDNF gene (brain-derived neurotrophic factor, BDNF) in the Czech population. The p.Val66Met (rs6265) polymorphism in the BDNF gene is associated with impaired intracellular trafficking and secretion of BDNF. Alterations in BDNF expression and function are involved in different brain disorders and represent a major downstream mechanism for stress response. Material and methods: Retrospectively, 317 DNA control samples of Czech individuals aged between 45 and 81 years (173 men and 144 women), were examined for p.Val66Met polymorphism in the BDNF gene using the melting analysis. Results: Frequency of the mutant allele (A) was 16.3% and it was 83.7% for the wild type allele (G). Conclusion: The requency of the p.Val66Met polymorphism in the BDNF gene in the Czech population was determined.
- MeSH
- Adult MeSH
- Genotype MeSH
- Polymorphism, Single Nucleotide * MeSH
- Clinical Studies as Topic MeSH
- Middle Aged MeSH
- Humans MeSH
- Brain-Derived Neurotrophic Factor * genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Geographicals
- Czech Republic MeSH
Mutations in the 5'-regulatory region of BCL6 were suggested to play a role in non-Hodgkin's lymphoma (NHL) progression and in the transformation of follicular lymphoma to more aggressive diffuse large B-cell type. The aim of this study was to explore association between polymorphism G397C in the 5'-region of BCL6 and both incidence and progression of NHL in 154 NHL cases and 362 controls. Neither frequencies of the rare BCL6 allele 397C nor particular genotypes differed significantly between NHL cases and controls. There was no significant association of histological type of NHL and clinical characteristics with this polymorphism.
This paper reports an approach to detection of single nucleotide polymorphism based on special amplification assay and surface plasmon resonance biosensor technology. In this assay, a part of the target DNA is recognized by a probe (probe A) coupled with streptavidin-oligonucleotide (SON) complexes ex situ, and when the mixture is injected in the sensor, another part of the target DNA is recognized by a DNA probe (probe B) immobilized on the sensor surface. To achieve high sensitivity and specificity, the assay is optimized in terms of composition of SON complexes, probe design, and assay temperature. It is demonstrated that this approach provides high specificity (no response to targets containing single-mismatched bases) and sensitivity (improves sensor response to perfectly matched oligonucleotides by one order of magnitude compared to the direct detection method). The assay is applied to detection of a short synthetic analogue of TP53 containing a "hot spot"-single nucleotide mismatch frequently mutated in germ line cancer-at levels down to 40 pM.
- MeSH
- Biosensing Techniques methods MeSH
- Molecular Diagnostic Techniques methods MeSH
- DNA Probes genetics MeSH
- DNA genetics MeSH
- Genes, p53 genetics MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Humans MeSH
- Oligonucleotides genetics MeSH
- Surface Plasmon Resonance instrumentation methods MeSH
- Sensitivity and Specificity MeSH
- Streptavidin chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Polymorphism, Single Nucleotide immunology MeSH
- Complement C1 genetics immunology MeSH
- Humans MeSH
- Sarcoidosis, Pulmonary genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Congress MeSH
- Geographicals
- Italy MeSH
Monocyte chemoattractant protein (MCP)-1 is the key chemokine in the process of atheroslerotic vascular inflammation. Examining already reported association between coronary artery disease (CAD) and the SNP A/G in the MCP-1 gene (position -2518), 139 Czech patients with CAD manifested as myocardial infarction (MI) and 359 unrelated healthy control (C) subjects were genotyped by PCR-SSP. Genotype and allele frequencies were not different in MI and C groups (allele G: MI, 20.5%; C, 23.8%, OR = 0.8, P > 0.05). No differences were detected when the patients were subdivided based on sex or the age of MI first occurrence. Further, no relationship was observed between circulating MCP-1 levels and carriage of the G allele. The data do not support a role for the MCP-1 -2518 single nucleotide polymorphism in susceptibility to CAD manifested by myocardial infarction.
- MeSH
- Alleles MeSH
- Chemokine CCL2 genetics immunology MeSH
- Financing, Organized MeSH
- Genetic Predisposition to Disease genetics MeSH
- Myocardial Infarction genetics immunology MeSH
- Polymorphism, Single Nucleotide genetics immunology MeSH
- Coronary Disease genetics immunology MeSH
- Middle Aged MeSH
- Humans MeSH
- Predictive Value of Tests MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- MeSH
- Adult MeSH
- Polymorphism, Single Nucleotide MeSH
- Colorectal Neoplasms genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Matrix Metalloproteinase 1 genetics metabolism MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Geographicals
- Czech Republic MeSH
Single-nucleotide polymorphisms (SNPs) have been shown to influence Fcγ receptor (FcγR) affinity and activity, but their effect on treatment response is unclear. We assessed their importance in the efficacy of obinutuzumab or rituximab combined with chemotherapy in untreated advanced follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) in the GALLIUM (www.clinicaltrials.gov #NCT01332968) and GOYA (#NCT01287741) trials, respectively. Genomic DNA was extracted from patients enrolled in GALLIUM (n = 1202) and GOYA (n = 1418). Key germline SNPs, FCGR2A R131H (rs1801274), FCGR3A F158V (rs396991), and FCGR2B I232T (rs1050501), were genotyped and assessed for their impact on investigator-assessed progression-free survival (PFS). In both cohorts there was no prognostic effect of FCGR2A or FCGR3A. In FL, FCGR2B was associated with favorable PFS in univariate and multivariate analyses comparing I232T with I232I, with a more modest association for rituximab-treated (univariate: hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.54-1.14; P = .21) vs obinutuzumab-treated patients (HR, 0.56; 95% CI, 0.34-0.91; P = .02). Comparing T232T with I232I, an association was found for obinutuzumab (univariate: HR, 2.76; 95% CI, 1.02-7.5; P = .0459). Neither observation retained significance after multiple-test adjustment. FCGR2B was associated with poorer PFS in multivariate analyses comparing T232T with I232I in rituximab- but not obinutuzumab-treated patients with DLBCL (HR, 4.40; 95% CI, 1.71-11.32; P = .002; multiple-test-adjusted P = .03); however, this genotype was rare (n = 13). This study shows that FcγR genotype is not associated with response to rituximab/obinutuzumab plus chemotherapy in treatment-naive patients with advanced FL or DLBCL.
- MeSH
- Lymphoma, Follicular * drug therapy MeSH
- Antibodies, Monoclonal, Humanized MeSH
- Polymorphism, Single Nucleotide MeSH
- Humans MeSH
- Nucleotides therapeutic use MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Receptors, IgG * genetics MeSH
- Rituximab therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Mucins and their glycosylation have been suggested to play an important role in colorectal carcinogenesis. We examined potentially functional genetic variants in the mucin genes or genes involved in their glycosylation with respect to colorectal cancer (CRC) risk and clinical outcome. We genotyped 23 single nucleotide polymorphisms (SNPs) covering 123 SNPs through pairwise linkage disequilibrium (r2>0.80) in the MUC1, MUC2, MUC4, MUC5AC, MUC6, and B3GNT6 genes in a hospital-based case-control study of 1532 CRC cases and 1108 healthy controls from the Czech Republic. We also analyzed these SNPs in relation to overall survival and event-free survival in a subgroup of 672 patients. Among patients without distant metastasis at the time of diagnosis, two MUC4 SNPs, rs3107764 and rs842225, showed association with overall survival (HR 1.40, 95%CI 1.08-1.82, additive model, log-rank p = 0.004 and HR 0.64, 95%CI 0.42-0.99, recessive model, log-rank p = 0.01, respectively) and event-free survival (HR 1.31, 95%CI 1.03-1.68, log-rank p = 0.004 and HR 0.64, 95%CI 0.42-0.96, log-rank p = 0.006, respectively) after adjustment for age, sex and TNM stage. Our data suggest that genetic variation especially in the transmembrane mucin gene MUC4 may play a role in the survival of CRC and further studies are warranted.
- MeSH
- Progression-Free Survival MeSH
- Adult MeSH
- Genotype MeSH
- Glycosylation MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Kaplan-Meier Estimate MeSH
- Colorectal Neoplasms genetics mortality pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Mucin-4 genetics metabolism MeSH
- Mucins genetics metabolism MeSH
- Biomarkers, Tumor genetics MeSH
- Colonic Neoplasms genetics mortality pathology MeSH
- Disease-Free Survival MeSH
- Risk Factors MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Linkage Disequilibrium MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
