scholarly journals CDKN2B gene rs1063192 polymorphism decreases the risk of glaucoma

Oncotarget ◽  
2017 ◽  
Vol 8 (13) ◽  
pp. 21167-21176 ◽  
Author(s):  
Zhenxian Hu ◽  
Chenliang He
Keyword(s):  
Cdkn2b Gene

CDKN2B gene expression is affected by 9p21.3 rs10757278 in CAD patients, six months after the MI

2019 ◽  
Vol 73 ◽  
pp. 70-76
Author(s):  
Ivan Zivotić ◽  
Tamara Djurić ◽  
Aleksandra Stanković ◽  
Dejan Milasinovic ◽  
Goran Stankovic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cdkn2b Gene

scholarly journals Quantitative High-Resolution CpG Island Mapping with Pyrosequencing™ Reveals Disease-Specific Methylation Patterns of the CDKN2B Gene in Myelodysplastic Syndrome and Myeloid Leukemia

2007 ◽  
Vol 53 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Kai Brakensiek ◽  
Luzie U Wingen ◽  
Florian Länger ◽  
Hans Kreipe ◽  
Ulrich Lehmann
Keyword(s):  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Cpg Island ◽  
Methylation Status ◽  
Low Grade ◽  
Myeloid Malignancies ◽  
Cpg Sites ◽  
Methylation Patterns ◽  
Cdkn2b Gene ◽  
Disease Specific

Abstract Background: Gene silencing through aberrant CpG island methylation is the most extensively analyzed epigenetic event in human tumorigenesis and has huge diagnostic and prognostic potential. Methylation patterns are often very heterogeneous, however, presenting a serious challenge for the development of methylation assays for diagnostic purposes. Methods: We used Pyrosequencing™ technology to determine the methylation status of 68 CpG sites in the CpG island of the CDKN2B gene [cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)], frequently hypermethylated in myeloid malignancies, in a series of bone marrow samples from patients with myelodysplasia and myeloid leukemia (n = 82) and from 32 controls. A total of 7762 individual methylation sites were quantitatively evaluated. Precision and reproducibility of the quantification was evaluated with several overlapping primers. Results: The use of optimized sequencing primers and the new Pyro Q-CpG™ software enabled precise and reproducible quantification with a single sequencing primer of up to 15 CpG sites distributed over ∼100 bp. Extensive statistical analyses of the whole CpG island revealed for the first time disease-specific methylation patterns of the CDKN2B gene in myeloid malignancies and small regions of differential methylation with high discriminatory power that enabled differentiation of even low-grade myelodysplastic syndrome samples from the controls, a result that was confirmed in an independent group of 9 control and 36 patient samples. Conclusion: The precise quantitative methylation mapping of whole CpG islands is now possible with Pyrosequencing software in combination with optimized sequencing primers. This method reveals disease-specific methylation patterns and enables the development of specific diagnostic assays.

scholarly journals CDKN2B Gene

2020 ◽  
Author(s):  
Keyword(s):  
Cdkn2b Gene

P3601Association of cdkn2b rs2891168 polymorphism with wall motion index score and the development of major adverse cardiovascular events within one year following ST elevation myocardial infarction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F A Magamedkerimova ◽  
F A Magamedkerimova ◽  
E N Ivantsov ◽  
N R Khasanov ◽  
E V Valeeva ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Wall Motion ◽  
St Elevation Myocardial Infarction ◽  
Major Adverse Cardiovascular Events ◽  
Kaplan Meier ◽  
St Elevation ◽  
One Year ◽  
The One ◽  
Cdkn2b Gene

Abstract Introduction According to the GRACE registry the largest amount of deaths occurs in the first year after ST elevation myocardial infarction (STEMI). Purpose To investigate the incidence of Major Adverse Cardiovascular Events (MACE), which include cardiovascular death, nonfatal myocardial infarction, nonfatal stroke one year after STEMI and Wall Motion Index Score (WMSI) in patients with different genotypes A/G of rs2891116 polymorphism in CDKN2B gene. Materials and methods A total of 141 patients, diagnosed with STEMI based on the Third Universal Definition of Myocardial Infarction (ESC, 2013) were included in the study, composed of 52 females and 89 males. The study group mean age was 63.8±11.8 years. Informed consent was obtained. During hospitalization echocardiography was performed and a blood sample was taken for genetic testing. Over the one-year period MACE were recorded. 17 patients were lost to follow up. Data was analysed using Kaplan-Meier estimator; to compare differences between groups log-rank test was applied; continuous data analysis was performed by Mann-Whitney test. The measured genotype frequencies fit the Hardy-Weinberg equilibrium (p>0.05). Results Kaplan-Meier survival analysis revealed that in patients with AA genotype the proportion of individuals who experienced MACE over the one year period after STEMI was higher in comparison with AG genotype carriers (log rank p=0.022). Participants with GG genotype did not show significant differences compared to other genotypes carriers (Picture 1). WMSI value in patients with AA genotype was higher (Me = 1.25; Q(0.25) = 1.13; Q(0.75) = 1.56) than in AG genotype carriers (Me = 1.13; Q(0.25) = 1.13; Q(0.75) = 1.25; p=0.037). In participants with GG genotype compared to AA and AG the WMSI value was not significantly different (Me = 1.19; Q(0.25) = 1.13; Q(0.75) = 1.32). Picture 1 Conclusions Genotype AA in CDKN2B gene rs2891168 in patients after STEMI is associated with higher probability of the development of MACE over the one year period after the index event, compared to AG genotype carriers. Participants with AA genotype exhibited a higher WMSI value after STEMI compared to patients with AG genotype.

Can Gene Methylation, Telomere Length and Activity of Telomerase Help with Individual Risk and Treatment Strategy of MDS Patients?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5087-5087
Author(s):  
Hana Cechova ◽  
Sona Vcelikova ◽  
Hana Lastuvkova ◽  
Martina Skalova ◽  
Zuzana Zemanova ◽  
...  
Keyword(s):  
Telomere Length ◽  
Treatment Strategy ◽  
Methylation Status ◽  
Telomerase Activity ◽  
Individual Risk ◽  
Significant Heterogeneity ◽  
Aberrant Methylation ◽  
Gene Methylation ◽  
Significant Difference ◽  
Cdkn2b Gene

Abstract Background: Epigenetic de novo methylation of CpG-rich areas located in the promotors of gene p15INK4b (CDKN2B) as it is capable to silence tumor suppressor genes and knowledge of telomere-telomerase complex may bring an important sign into molecular backround of malignant transformation in patients with myelodysplastic syndromes (MDS). Aims: Intensity of gene methylation, the variability of telomere length (TRF) and telomerase activity (TA) were studied in bone marrow (BM) or peripheral blood (PB) cells of patients with MDS before treatment and during the course of the disease to evaluate its prognostic significance and association with clinical outcomes and disease progression. Methods: 110 patients with MDS were stratiffied according to the WHO classification: 18 × RA, 3 × RARS, 32 × RCMD, 12 × 5q-syndrome, 17 × RAEB1, 19 × RAEB2 and 9 × MDS/MPS. BM cells from 30 age matched healthy donors served as controls, 5 leukemic cell lines were examined as positive controls. The level of DNA methylation was quantified by methylation specific PCR after sodium bisulphate modification of DNA, CpGenom DNA Modification kit from Scintila. The methylation status was dedicated as Methylation Indices (MI) in the range 0.0–1.0. The telomere length was determined as terminal restriction fragment (TRF index in kbp) after Southern analysis of genomic DNA, TeloTAGGG Telomere Length Assay kit from Roche. The activity of telomerase was assessed by Quantitative TRAP assay based on a photometric enzyme immunoassay on solid phase, Telo TAGGG Telomerase PCR Elisa plus kit from Roche. We postulated TRF shorter than 7.5 kbp as reduced telomeres and values of TA higher than 0.0263 as positive telomerase activity. Results: Aberrant methylation of CDKN2B gene was present in 64% of MDS untreated patients showing significant heterogeneity in WHO subgroups. Mean values of MI increased as follows: from 0.18 ± 0.13 in RCMD, 0.21 ± 0.11 in RA/RARS, 0.26 ± 0.19 in 5q- syndrome, 0.33 ± 0.17 in RAEB1, 0.34 ± 0.17 in RAEB2, up to 0.41 ± 0.14 in MDS/MPS. A significant difference was found between early forms of MDS (RA/RARS, RCMD, 5q-syndrome) and advanced MDS with excess of blasts (RAEB1, RAEB2, MDS/MPS). High level of methylation CDKN2B gene was observed in 70% (33/47) of patients with advances forms of MDS (MI=0.36 ± 0.17) in comparison with early phases of MDS (MI=0.20 ± 0.14) in 60% (39/65) of patients. In one patient with RAEB2, a significant decrease in MI from 0.44 in BM and 0.37 in PB to 0,25 to 0,04, respectively was observed after 3 months of treatment with decitabine together with simultaneous prolongation of TRF from 7,62 kbp to 10.5 kbp. The patient achieved partial remission of the disease after 6 months of treatment with corresponding values of MI=0.20 and TRF=9.63kbp. In another patient, a progression of the disease from RCMD towards RAEB was connected vith increase in MI from 0.00 to 0.39 that correlated with elevation of telomerase activity from 0 to 0.0534. Conclusions: The results confirm association of aberrant gene methylation with progression of early MDS to advanced forms with excess of blasts. Our findings also showed a certain degree of correlation between molecular changes in gene methylation, telomere length and telomerase activity in different phases of disease. Thus, determination of these markers may contribute to more precise estimation of an individual MDS patient’s risk and for decision of an optimal treatment strategy.

Functional polymorphisms in the CDKN2A- CDKN2B gene regions affect pancreatic cancer risk

Pancreatology ◽  
2016 ◽  
Vol 16 (3) ◽  
pp. S25
Author(s):  
Daniele Campa ◽  
Manuela Pastore ◽  
Manuel Gentiluomo ◽  
Raffaele Pezzilli ◽  
Ugo Boggi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Risk ◽  
Pancreatic Cancer Risk ◽  
Functional Polymorphisms ◽  
Cdkn2b Gene

scholarly journals Disulfiram May Contribute to Apoptosis of Myeloma Cells By Reactivating of Cell Cycle Regulating Gene CDKN2A

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5125-5125
Author(s):  
Denisa Hrckova Drozdkova ◽  
Jan Gursky ◽  
Petra Luzna ◽  
Sabina Sevcikova ◽  
Jiri Minarik ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Caspase 3 ◽  
Nucleoside Analogs ◽  
The Other ◽  
Cdk Inhibitors ◽  
Myeloma Cells ◽  
Cdkn2a Gene ◽  
U266 Cell ◽  
Apoptotic Effect ◽  
Cdkn2b Gene

Abstract Objective: Multiple myeloma (MM) is an incurable plasma-cell dyscrasia characterized by uncontrolled growth of malignant plasma cells in the bone marrow. Proteasome inhibitor bortezomib is a frontline MM drug, however acquired resistance to bortezomib remains a clinical hurdle. Disulfiram (tetraethylthiuram disulfide, DSF) belongs to promising cancer-killing drugs, and although the mechanism of its anticancer activity remains unclear, it has been suggested that this drug inhibits proteasome activity. Furthermore, disulfiram contains strong thio-reactive functional groups and since the catalytic mechanism of DNA methyltransferases (DNMTs) involves the covalent attack at the C6 position of cytosine by the thiol group of the catalytic cysteine on the DNMT enzyme, the DSF can function as DNMT non-nucleoside inhibitor with possible gene demethylation´s effect. On the other hand, DNMT inhibitors, 5-azacytidine (AZA) and 5-aza-2´-deoxycytidine (DAC) are nucleoside analogs, whose mechanism of action involves incorporation of the aza-modified base into DNA during DNA synthesis with subsequent covalent trapping of the DNMT enzyme. Therefore, these nucleoside analogs (AZA and DAC) can have significant cytotoxicity and can lead to major adverse effects, including myelosuppression, when administered to patients. Methods: RPMI8226 and U266 myeloma cells were exposed to DSF (0, 1 µM and 1 µM), DAC (0, 5 µM, 3, 75 µM and 5 µM), JNJ-7706621 (0, 5 µM and 5 µM) and 5 µM SAHA (suberoylanilide hydroxamic acid). Subsequently, we assessed for: i/ cell viability assay using 3-(4, 5dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide agent (MTT); ii/ DNA content by flow cytometry analysis; iii/ apoptosis determination by Annexin V and activity of caspase-3 and -7 quantification by cleavage of fluorogenic substrate CellEvent™ Caspase-3/7 Green Detection Reagent; iii/ CDKN2A and CDKN2B methylation status by methylation-specific PCR and pyrosequencing; iiii/ CDKN2A and CDKN2B gene expression analysis by quantitative RT-PCR. Results: To determine the influence of DSF, DAC and two cyclin dependent kinase (CDK) inhibitors JNJ-7706621 and SAHA on cell cycle regulation, RPMI8226 and U266 cell lines were treated with the same scheme as for methylation and expression analysis. U266 cell treatments with 1 µM DSF (18, 9 %) and 5 µM JNJ (21, 6 %) show similar parameters in sub-G1 cell population, but lower when they compared to SAHA treatment (29, 7 %). Analysis of apoptosis of cells treated with 1 µM DSF show 18,51 % of apoptotic cells, while 26,22 % and 28,4 % apoptotic cells after 5 µM SAHA and 5 µM JNJ treatments were detected. The proportions of cells in apoptosis in both 0, 1 µM and 1 µM DSF treatments are 21,8 % and 18,5 %. We have found unmethylated 162 bp CDKN2B analysed gene region, while 150 bp analysed CDKN2A gene region is methylated. Unmethylated state of the CDKN2B gene was confirmed by pyrosequencing of 223 bp promoter and 138 bp 1.exon gene regions. Expression of the unmethylated CDKN2B gene is not influenced, while the 0,1 µM DSF treatment causes increased expression of the CDKN2A gene (Graph1). Conclusion: In treated myeloma cells, we have examined apoptotic effect of DSF in comparison to CDK inhibitors JNJ-06621 and SAHA through detection of methylation and expression status of CDKN2A and CDKN2B genes. Our results indicate DSF pro-apoptotic effect comparable to used CDK inhibitors. The 5-aza-2´-deoxycytidine with demethylation activity and DSF do not affect an expression of the unmethylated CDKN2B gene, its expression effectively increases CDK inhibitors (Graph2). On the other hand, the expression of the methylated CDKN2A gene is only slightly increased in DSF treated cells in comparison to other treatments. This study was supported in part by NV18-03-0050 from the Ministry of Health of the Czech Republic and LF_2018_001 from Palacky University Olomouc. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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