• MeSH
• cytotoxické testy imunologické MeSH
• fenotyp MeSH
• geny MeSH
• isoantigeny analýza   MeSH
• zdravotnické přehledy MeSH

• MeSH
• frekvence genu analýza   MeSH
• populační genetika analýza   MeSH
• testování histokompatibility využití   MeSH

• MeSH
• cystická fibróza diagnóza   MeSH
• DNA analýza   MeSH
• lidé MeSH
• pot analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• kazuistiky MeSH

Genome-wide association studies (GWASs) based on common single nucleotide polymorphisms (SNPs) have identified several loci associated with the risk of monoclonal gammopathy of unknown significance (MGUS), a precursor condition for multiple myeloma (MM). We hypothesized that analyzing haplotypes might be more useful than analyzing individual SNPs, as it could identify functional chromosomal units that collectively contribute to MGUS risk. To test this hypothesis, we used data from our previous GWAS on 992 MGUS cases and 2910 controls from three European populations. We identified 23 haplotypes that were associated with the risk of MGUS at the genome-wide significance level (p < 5 × 10-8) and showed consistent results among all three populations. In 10 genomic regions, strong promoter, enhancer and regulatory element-related histone marks and their connections to target genes as well as genome segmentation data supported the importance of these regions in MGUS susceptibility. Several associated haplotypes affected pathways important for MM cell survival such as ubiquitin-proteasome system (RNF186, OTUD3), PI3K/AKT/mTOR (HINT3), innate immunity (SEC14L1, ZBP1), cell death regulation (BID) and NOTCH signaling (RBPJ). These pathways are important current therapeutic targets for MM, which may highlight the advantage of the haplotype approach homing to functional units.

• MeSH
• celogenomová asociační studie * MeSH
• genetická predispozice k nemoci * MeSH
• haplotypy * MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• mnohočetný myelom genetika   MeSH
• monoklonální gamapatie nejasného významu * genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• buněčné klony MeSH
• imunogenetika MeSH
• protilátky MeSH

The analysis of 21 families affected with classical phenylketonuria (PKU) from the Moravian area of Czechoslovakia has revealed 12 different RFLP haplotypes. Nine and eight haplotypes were associated with the normal and with the mutant alleles, respectively. Most normal alleles are associated with haplotype 1 (42.9%). Almost 80% of all mutant alleles are confined within only three haplotypes (1, 2 and 4). There was a strong association between haplotype 2 and the Czech mutant alleles (61.9% of the mutant alleles compared with 4.8% of the normal alleles). There was linkage disequilibrium between this haplotype and the R408W mutation in exon 12. Two mutant haplotypes 7 were found and in both cases they were tightly linked with G272ter mutation. Our finding is in agreement with observations in other Eastern European countries. These data provide further support for the theories of the spread of the R408W mutation from east to west in European populations.

• MeSH
• fenylalaninhydroxylasa genetika   MeSH
• fenylketonurie genetika   MeSH
• genetická vazba MeSH
• haplotypy MeSH
• lidé MeSH
• mutace MeSH
• polymorfismus délky restrikčních fragmentů MeSH
• Check Tag
• lidé MeSH
• Geografické názvy
• Československo MeSH

Nitric oxide (NO) is an important mediator of physiologic processes in the airways. Evidence exists that genetic factors affect NO formation and contribute to the pathophysiology of asthma. The aims of this study were to determine the endothelial NO synthase (eNOS) haplotypes in Czech asthmatics and control subjects and examine their relation to asthma. We analyzed a total of six polymorphisms. Two SNPs in the promoter (C-786T and C-691T), two variants in the introns (27-bp repeat in intron 4 and G11T in intron 23), and two others in the exons (C774T in exon 6 and G894T in exon 7) were genotyped in 610 subjects (asthma, n = 294; healthy controls, n = 316), and a case-control association study was conducted. No significant differences in allele or genotype frequencies for individual polymorphisms were observed between patients with asthma and controls after correction for multiple comparisons. Nevertheless, a G to T exchange in intron 23 was related with specific sensitization for feather (p = 0.008, p(corr) < 0.05). However, the common haplotype -786T/-691C/27-bp 5 repeat variant/774C/894G/11T was associated with lower risk of asthma (p = 0.001, p(corr) < 0.05, odds ratio = 0.58, 95% confidence interval = 0.46-0.73). These findings suggest that endothelial NOS variants may be one of the factors participating in protection or susceptibility to asthma in our population.

• MeSH
• bronchiální astma epidemiologie   genetika   MeSH
• dospělí MeSH
• financování organizované MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• haplotypy MeSH
• interval spolehlivosti MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• odds ratio MeSH
• rizikové faktory MeSH
• sekvenční analýza DNA MeSH
• studie případů a kontrol MeSH
• synthasa oxidu dusnatého, typ III genetika   MeSH
• vazebná nerovnováha MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND AND OBJECTIVE: Membrane solute carrier transporters play an important role in the transport of a wide spectrum of substrates including anticancer drugs and cancer-related physiological substrates. This study aimed to assess the prognostic relevance of gene expression and genetic variability of selected solute carrier transporters in breast cancer. METHODS: Gene expression was determined by quantitative real-time polymerase chain reaction. All SLC46A1 and SLCO1A2 exons and surrounding non-coding sequences in DNA extracted from the blood of patients with breast cancer (exploratory phase) were analyzed by next-generation sequencing technology. Common variants (minor allele frequency ≥ 5%) with in silico-predicted functional relevance were further analyzed in a large cohort of patients with breast cancer (n = 815) and their prognostic and predictive potential was estimated (validation phase). RESULTS: A gene expression and bioinformatics analysis suggested SLC46A1 and SLCO1A2 to play a putative role in the prognosis of patients with breast cancer. In total, 135 genetic variants (20 novel) were identified in both genes in the exploratory phase. Of these variants, 130 were non-coding, three missense, and two synonymous. One common variant in SLCO1A2 and four variants in SLC46A1 were predicted to be pathogenic by in silico programs and subsequently validated. A SLC46A1 haplotype block composed of rs2239911-rs2239910-rs8079943 was significantly associated with ERBB2/HER2 status and disease-free survival of hormonally treated patients. CONCLUSIONS: This study revealed the prognostic value of a SLC46A1 haplotype block for breast cancer that should be further studied.

• MeSH
• analýza přežití MeSH
• folátový přenašeč spřažený s transportem protonů genetika   MeSH
• genetická variace * MeSH
• haplotypy MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory prsu genetika   MeSH
• přenašeče organických aniontů genetika   MeSH
• prognóza MeSH
• regulace genové exprese u nádorů MeSH
• sekvenční analýza DNA MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Superoxide produced by airway epithelial and inflammatory cells may contribute to the pathogenesis of asthma. NADPH oxidase (an enzyme complex made up of 5 subunits) is a major source of superoxide in cells. We sought to elucidate the role of genetic variability in the gene encoding the p22(phox) subunit of the NADPH oxidase (CYBA, 16q24.3) in asthma susceptibility by means of an association study of haplotypes based on 3 common single nucleotide polymorphisms (SNPs), -930A/G, 242C/T (H72Y) and 640A/G. METHODS: SNPs were genotyped by PCR-RFLP methods in a cohort of age- and sex-matched subjects with bronchial asthma (n = 305) and healthy controls (n = 311). Haplotypes were constructed in silico using a Monte Carlo-based algorithm. Furthermore, association of SNPs with sensitization to selected allergens (total 15 tested by skin prick test positivity/negativity) was analyzed. RESULTS: In a single locus analysis, SNPs 242C/T and 640A/G were marginally significantly associated with asthma (p = 0.036 and 0.036, respectively). SNP 640A/G showed a significant association with sensitization to 2 allergens tested (p(corr) < 0.02). Haplotype analysis identified a total of 8 haplotypes with population frequencies from 0.07 to 0.22. Distribution of haplotypes significantly differed between cases and controls (omnibus p = 0.017, 10,000 permutations). In the post-hoc analysis, haplotype CYBA(3) (-930G/242T/640A) was associated with an increased risk of asthma (p(corr) < 0.05; OR = 1.43, 95% CI 1.06-1.93). CONCLUSIONS: This study supports the hypothesis that genetic variability in the CYBA gene probably contributes to the susceptibility to bronchial asthma (or its related phenotypes) in our population

• MeSH
• alergeny imunologie   MeSH
• bronchiální astma genetika   imunologie   MeSH
• dospělí MeSH
• financování organizované MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• haplotypy MeSH
• jednonukleotidový polymorfismus MeSH
• kožní testy MeSH
• lidé středního věku MeSH
• lidé MeSH
• NADPH-oxidasy genetika   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

The interleukin-18 (IL-18) gene on chromosome 11q22 has been suggested as a susceptibility factor for allergies. To test for a possible role of IL-18 polymorphisms in Czech population, case-control study including 958 subjects (633 allergic patients and 325 healthy controls) was performed. An allele-specific polymerase chain reaction was used to analyze variants at positions -607 C/A (rs1946518) and -137 G/C (rs187238) in the promoter region together with the polymerase chain reaction-restriction fragment length polymorphism method for the detection of polymorphism at position -140 C/G (previously -133 C/G, rs360721) in intron 1 of the IL-18 gene. The -1297 C/T (rs360719) polymorphism was genotyped by real-time-polymerase chain reaction, using a predevelopment TaqMan allele discrimination assay. There were no significant differences in distribution of alleles or genotypes in any of four single nucleotide polymorphisms in the IL-18 gene between controls and patients. However, subsequent analysis revealed a significant difference in haplotype frequencies between the allergic patients and healthy subjects (p < 0.01). Haplotype formed by -1297 C/-607 A/-137 C/-140 C alleles occurred significantly more frequently in patients than controls (0.0433 vs 0.0129; p < 0.0003; p(corr)< 0.01, OR = 3.37; 95% CI = 1.59-7.14). In contrast, there was no relationship among the IL-18 variants and total serum IgE level. Our results indicate that promoter polymorphisms in the IL-18 gene act in interaction and could play a role in allergic disorders.

• MeSH
• alergie genetika   imunologie   patofyziologie   MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• genetické asociační studie MeSH
• haplotypy MeSH
• interleukin-18 genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• letální geny MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutační analýza DNA MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH