BACKGROUND: In sarcoidosis, the direction and intensity of immunological reactions involved in disease pathophysiology is affected by variation in the genes coding for effector and regulatory molecules with immune functions. This study, therefore, investigates polymorphic variants in genes involved in inflammation, immune reactions, and granuloma formation in context of their plausible association with sarcoidosis, with specific focus on Greek population. METHODS: A total of 18 single-nucleotide polymorphisms (SNPs) were genotyped in Greek patients with pulmonary sarcoidosis (n = 103) and in healthy Greek control subjects (n = 100) using multiplexed MassARRAY (MassARRAY ®) iPLEX assay based on MALDI-TOF mass spectrometry. RESULTS: TGF-β3 rs3917200*G variant was associated with sarcoidosis (OR: 3.04 [95% CI: 1.98-4.69], p = 2.76*10-7). Further, ANXA11 rs1049550*A variant was associated with sarcoidosis (OR: 0.59 [0.39-0.89], p = 0.01). CONCLUSIONS: This first study of genetic variation of immune-related genes in Greek patients with sarcoidosis brings to attention a novel disease 'susceptibility' factor: TGF-β3 rs3917200*G allele. It also confirms previously reported 'protective' association between sarcoidosis and functional variant ANXA11 rs1049550*A. Further work is required to validate these findings and to expand investigation of their plausible relationship with clinical course of the disease.

• MeSH
• alely MeSH
• annexiny genetika   MeSH
• běloši genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci * MeSH
• genotypizační techniky MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• plicní sarkoidóza genetika   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transformující růstový faktor beta3 genetika   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
• Geografické názvy
• Řecko MeSH

Next-generation sequencing (NGS) is increasingly used in transplantation settings, but also as a method of choice for in-depth analysis of population-specific HLA genetic architecture and its linkage to various diseases. With respect to complex ethnic admixture characteristic for East Croatian population, we aimed to investigate class-I (HLA-A, -B, -C) and class-II (HLA-DRB1, -DQA1, -DQB1) HLA diversity at the highest, 4-field resolution level in 120 healthy, unrelated, blood donor volunteers. Genomic DNA was extracted and HLA genotypes of class I and DQA1 genes were defined in full-length, -DQB1 from intron 1 to 3' UTR, and -DRB1 from intron 1 to intron 4 (Illumina MiSeq platform, Omixon Twin algorithms, IMGT/HLA release 3.30.0_5). Linkage disequilibrium statistics, Hardy-Weinberg departures, and haplotype frequencies were inferred by exact tests and iterative Expectation-Maximization algorithm using PyPop 0.7.0 and Arlequin v3.5.2.2 software. Our data provide first description of 4-field allele and haplotype frequencies in Croatian population, revealing 192 class-I and class-II alleles and extended haplotypic combinations not apparent from the existing 2-field HLA reports from Croatia. This established reference database complements current knowledge of HLA diversity and should prove useful in future population studies, transplantation settings, and disease-associated HLA screening.

• MeSH
• běloši genetika   MeSH
• dárci krve MeSH
• dospělí MeSH
• frekvence genu MeSH
• haplotypy MeSH
• HLA-A antigeny genetika   MeSH
• HLA-B antigeny genetika   MeSH
• HLA-C antigeny genetika   MeSH
• HLA-DQ alfa řetězec genetika   MeSH
• HLA-DQ beta řetězec genetika   MeSH
• HLA-DRB1 řetězec genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• sekvenční analýza DNA MeSH
• vazebná nerovnováha MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Chorvatsko MeSH

BACKGROUND: Several studies indicated that antipsychotic treatment response and side effect manifestation can be different due to inter-individual variability in genetic variations. AIM OF THE STUDY: Here we perform a case-control study to explore a potential association between schizophrenia and variants within the antipsychotic drug molecular targets (DRD1, DRD2, DRD3, HTR2A, HTR6) and metabolizing enzymes (CYP2D6, COMT) genes in Armenian population including also analysis of their possible relationship with disease clinical symptoms. METHODS: A total of 18 SNPs was studied in patients with schizophrenia (n = 78) and healthy control subjects (n = 77) using MassARRAY genotyping. RESULTS: We found that two studied genetic variants, namely DRD2 rs4436578*C and HTR2A rs6314*A are underrepresented in the group of patients compared to healthy subjects. After the correction for multiple testing, the rs4436578*C variant remained significant while the rs6314*A reported borderline significance. No significant differences in minor allele frequencies for other studied variants were identified. Also, a relationship between the genotypes and age of onset as well as disease duration has been detected. CONCLUSIONS: The DRD2 rs4436578*C genetic variant might have protective role against schizophrenia, at least in Armenians.

• MeSH
• antipsychotika terapeutické užití   MeSH
• cytochrom P-450 CYP2D6 genetika   MeSH
• dopamin genetika   metabolismus   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus * MeSH
• katechol-O-methyltransferasa genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolické sítě a dráhy genetika   MeSH
• mladý dospělý MeSH
• receptory dopaminové genetika   MeSH
• receptory serotoninové genetika   MeSH
• schizofrenie farmakoterapie   genetika   MeSH
• senioři MeSH
• serotonin genetika   metabolismus   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

Over a half million new cases of Head and Neck Squamous Cell Carcinoma (HNSCC) are diagnosed annually worldwide, however, 5 year overall survival is only 50% for HNSCC patients. Recently, high throughput technologies have accelerated the genome-wide characterization of HNSCC. However, comprehensive pipelines with statistical algorithms that account for HNSCC biology and perform independent confirmatory and functional validation of candidates are needed to identify the most biologically relevant genes. We applied outlier statistics to high throughput gene expression data, and identified 76 top-scoring candidates with significant differential expression in tumors compared to normal tissues. We identified 15 epigenetically regulated candidates by focusing on a subset of the genes with a negative correlation between gene expression and promoter methylation. Differential expression and methylation of 3 selected candidates (BANK1, BIN2, and DTX1) were confirmed in an independent HNSCC cohorts from Johns Hopkins and TCGA (The Cancer Genome Atlas). We further performed functional evaluation of NOTCH regulator, DTX1, which was downregulated by promoter hypermethylation in tumors, and demonstrated that decreased expression of DTX1 in HNSCC tumors maybe associated with NOTCH pathway activation and increased migration potential.

• MeSH
• dospělí MeSH
• epigenomika * MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA MeSH
• nádorové buněčné linie MeSH
• nádory hlavy a krku genetika   patologie   MeSH
• pohyb buněk genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• receptory Notch genetika   MeSH
• regulace genové exprese u nádorů * MeSH
• RNA interference MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• shluková analýza MeSH
• signální transdukce genetika   MeSH
• spinocelulární karcinom genetika   patologie   MeSH
• stanovení celkové genové exprese metody   MeSH
• tumor supresorové geny * MeSH
• ubikvitinligasy genetika   MeSH
• výpočetní biologie metody   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

Idiopathic pulmonary fibrosis (IPF) affects lung parenchyma with progressing fibrosis. In this study, we aimed to replicate MUC5B rs35705950 variants and determine new plausible candidate variants for IPF among four different European populations. We genotyped 26 IPF candidate loci in 165 IPF patients from four European countries, such as Czech Republic (n = 41), Germany (n = 33), Greece (n = 40), France (n = 51), and performed association study comparing observed variant distribution with that obtained in a genetically similar Czech healthy control population (n = 96) described in our earlier data report. A highly significant association for a promoter variant (rs35705950) of mucin encoding MUC5B gene was observed in all IPF populations, individually and combined [odds ratio (95% confidence interval); p-value as 5.23 (8.94-3.06); 1.80 × 10(-11)]. Another non-coding variant, rs7934606 in MUC2 was significant among German patients [2.85 (5.05-1.60); 4.03 × 10(-4)] and combined European IPF cases [2.18 (3.16-1.50); 3.73 × 10(-5)]. The network analysis for these variants indicated gene-gene and gene-phenotype interactions in IPF and lung biology. With replication of MUC5B rs35705950 previously reported in U.S. populations of European descent and indicating other plausible polymorphic variants relevant for IPF, we provide additional reference information for future extended functional and population studies aimed, ideally with inclusion of clinical parameters, at identification of IPF genetic markers.

• Publikační typ
• časopisecké články MeSH

• MeSH
• analýza přežití MeSH
• dospělí MeSH
• imunohistochemie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA MeSH
• nádorové biomarkery MeSH
• nemalobuněčný karcinom plic * genetika   metabolismus   patologie   MeSH
• P-glykoprotein metabolismus   MeSH
• prognóza MeSH
• proteiny spojené s mnohočetnou rezistencí k lékům metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• retrospektivní studie MeSH
• ribonukleoproteiny MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

Distribution of cytochrome P450 2C19 enzyme gene (CYP2C19) variants affecting metabolism of clopidogrel was determined in 526 Czech patients after percutaneous coronary intervention using MassARRAY genotyping and compared to distribution in other populations of European descent. Fifty-three (10%) patients underwent parallel determination of CYP2C19 genotypes from buccal swabs by a point of care technique with 100% concordance to the main genotyping platform. Observed CYP2C19 genotypes were related to clopidogrel metabolism phenotypes and discussed in population context. Hereby, presented methodologies provide accurate CYP2C19 genotyping results in a relatively short time of one up to 12 h and may, therefore, find the relevant place in the field of genotype-guided antiplatelet therapy.

• MeSH
• cytochrom P450 CYP2C19 genetika   MeSH
• dospělí MeSH
• farmakogenetika MeSH
• fenotyp MeSH
• genetická variace MeSH
• genotyp MeSH
• inhibitory agregace trombocytů terapeutické užití   MeSH
• koronární angioplastika škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tiklopidin analogy a deriváty   terapeutické užití   MeSH
• vyšetření u lůžka 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
• Geografické názvy
• Česká republika MeSH

• Publikační typ
• časopisecké články MeSH

Using high-throughput analyses and the TRANSFAC database, we characterized TF signatures of head and neck squamous cell carcinoma (HNSCC) subgroups by inferential analysis of target gene expression, correcting for the effects of DNA methylation and copy number. Using this discovery pipeline, we determined that human papillomavirus-related (HPV+) and HPV- HNSCC differed significantly based on the activity levels of key TFs including AP1, STATs, NF-κB and p53. Immunohistochemical analysis confirmed that HPV- HNSCC is characterized by co-activated STAT3 and NF-κB pathways and functional studies demonstrate that this phenotype can be effectively targeted with combined anti-NF-κB and anti-STAT therapies. These discoveries correlate strongly with previous findings connecting STATs, NF-κB and AP1 in HNSCC. We identified five top-scoring pair biomarkers from STATs, NF-κB and AP1 pathways that distinguish HPV+ from HPV- HNSCC based on TF activity and validated these biomarkers on TCGA and on independent validation cohorts. We conclude that a novel approach to TF pathway analysis can provide insight into therapeutic targeting of patient subgroup for heterogeneous disease such as HNSCC.

• MeSH
• infekce papilomavirem genetika   metabolismus   MeSH
• lidé MeSH
• metylace DNA MeSH
• nádorové buněčné linie MeSH
• nádory hlavy a krku genetika   metabolismus   virologie   MeSH
• NF-kappa B genetika   metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• signální transdukce MeSH
• spinocelulární karcinom genetika   metabolismus   virologie   MeSH
• transkripční faktor STAT3 genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH