The relationship between the prognosis of children with acute arterial stroke and polymorphisms of CDKN2B, HDAC9, NINJ2, NAA25 genes

Bozpolat, Adil; Ünal, Ekrem; Topaloglu, Tugba; Taheri, Serpil; Bayram, Ayşe Kaçar; Özcan, Alper; Karakükçü, Musa; Özdemır, Mehmet Akif; Per, Hüseyin

doi:10.1007/s11239-018-01802-9

Cited by 5 publications

(3 citation statements)

References 37 publications

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“…74 NINJ2 mRNA is overexpressed in whole blood according to the Genotype-Tissue Expression GTEx project. 60 DNA methylation of NINJ2 was proposed to be an multi-generationally inheritable epigenetic modification and environmentally induced in humans. 75 NINJ2 was also found to be differentially hypermethylated in an intron region overlapped by NINJ2-AS1 in whole blood of multiple sclerosis patients.…”

Section: Zinc Finger Protein 57 (Zfp57)mentioning

confidence: 99%

ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome‐wide DNA methylation pilot study

Hernández

Hernández-Castañeda

Pieschacón

et al. 2021

J of Periodontal Research

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Objective: To investigate the differences in the epigenomic patterns of DNA methylation in peripheral leukocytes between patients with periodontitis and gingivally healthy controls evaluating its functional meaning by functional enrichment analysis. Background:The DNA methylation profiling of peripheral leukocytes as immunerelated tissue potentially relevant as a source of biomarkers between periodontitis patients and gingivally healthy subjects has not been investigated.Methods: A DNA methylation epigenome-wide study of peripheral leukocytes was conducted using the Illumina MethylationEPIC platform in sixteen subjects, eight diagnosed with periodontitis patients and eight age-matched and sex-matched periodontally healthy controls. A trained periodontist performed the clinical evaluation.Global DNA methylation was estimated using methylation-sensitive high-resolution melting in LINE1. Routine cell count cytometry and metabolic laboratory tests were also performed. The analysis of differentially methylated positions (DMPs) and differentially methylated regions (DMRs) was made using R/Bioconductor environment considering leukocyte populations assessed in both routine cell counts and using the FlowSorted.Blood.EPIC package. Finally, a DMP and DMR intersection analysis was performed. Functional enrichment analysis was carried out with the differentially methylated genes found in DMP.Results: DMP analysis identified 81 differentially hypermethylated genes and 21 differentially hypomethylated genes. Importantly, the intersection analysis showed that zinc finger protein 718 (ZNF718) and homeobox A4 (HOXA4) were differentially hypermethylated and zinc finger protein 57 (ZFP57) was differentially hypomethylated in periodontitis. The functional enrichment analysis found clearly immune-related ontologies such as "detection of bacterium" and "antigen processing and presentation." Conclusion:The results of this study propose three new periodontitis-related genes: ZNF718, HOXA4, and ZFP57 but also evidence the suitability and relevance of studying leukocytes' DNA methylome for biological interpretation of systemic immunerelated epigenetic patterns in periodontitis. | 711 HERNÁNDEZ Et al.

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Section: Zinc Finger Protein 57 (Zfp57)mentioning

confidence: 99%

ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome‐wide DNA methylation pilot study

Hernández

Hernández-Castañeda

Pieschacón

et al. 2021

J of Periodontal Research

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“…Genetic variations in some genes (e.g., SLC22A7, ZNF318 and HDAC9) were also associated with ischemic stroke (5). In addition, IGFBP3 and HDAC9 have been found to be related to poor prognosis in patients with ischemic stroke (15)(16)(17). Therefore, the identified BP-related loci may contain genes involved in ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

Association of DNA Methylation in Blood Pressure-Related Genes With Ischemic Stroke Risk and Prognosis

Zhang

Wang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundA genome-wide association study identified 12 genetic loci influencing blood pressure and implicated a role of DNA methylation. However, the relationship between methylation and ischemic stroke has not yet been clarified. We conducted a large-sample sequencing study to identify blood leukocyte DNA methylations as novel biomarkers for ischemic stroke risk and prognosis based on previously identified genetic loci.MethodsMethylation levels of 17 genes were measured by sequencing in 271 ischemic stroke cases and 323 controls, and the significant associations were validated in another independent sample of 852 cases and 925 controls. The associations between methylation levels and ischemic stroke risk and prognosis were evaluated.ResultsMethylation of AMH, C17orf82, HDAC9, IGFBP3, LRRC10B, PDE3A, PRDM6, SYT7 and TBX2 was significantly associated with ischemic stroke. Compared to participants without any hypomethylated targets, the odds ratio (OR) (95% confidence interval, CI) for those with 9 hypomethylated genes was 1.41 (1.33–1.51) for ischemic stroke. Adding methylation levels of the 9 genes to the basic model of traditional risk factors significantly improved the risk stratification for ischemic stroke. Associations between AMH, HDAC9, IGFBP3, PDE3A and PRDM6 gene methylation and modified Rankin Scale scores were significant after adjustment for covariates. Lower methylation levels of AMH, C17orf82, PRDM6 and TBX2 were significantly associated with increased 3-month mortality. Compared to patients without any hypomethylated targets, the OR (95% CI) for those with 4 hypomethylated targets was 1.12 (1.08–1.15) for 3-month mortality (P = 2.28 × 10−10).ConclusionThe present study identified blood leukocyte DNA methylations as potential factors affecting ischemic stroke risk and prognosis among Han Chinese individuals.

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“…And rs11066150 A/G was an intron variant in N-alpha-acetyltransferase 25 (NAA25) gene (also known as MDM20, C12orf30 and NAP1). NAA25 gene variants were reported to be associated with type 1 diabetes (T1D), rheumatoid arthritis, acute arterial stroke and dyslipidemia (7)(8)(9)(10). However, the relationship between NAA25 and breast cancer is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of NAA25 Suppresses Breast Cancer Progression by Regulating Apoptosis and Cell Cycle

Zuo

et al. 2022

Front. Oncol.

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NAA25 gene variants were reported as risk factors for type 1 diabetes, rheumatoid arthritis and acute arterial stroke. But it’s unknown whether it could contribute to breast cancer. We identified rs11066150 in lncHSAT164, which contributes to breast cancer, in our earlier genome-wide long non-coding RNA association study on Han Chinese women. However, rs11066150 A/G variant is also located in NAA25 intron. Based on the public database, such as TCGA and Curtis dataset, NAA25 gene is highly expressed in breast cancer tissues and this result has also been proved in our samples and cell lines through RT-qPCR and western blot analysis. To better understand the function of NAA25 in breast cancer, we knocked down the expression of NAA25 in breast cancer cell lines, FACS was used to detect cell apoptosis and cell cycle and colony formation assay was used to detect cell proliferation. We found that NAA25-deficient cells could increase cell apoptosis, delay G2/M phase cell and decrease cell clone formation. RNA sequencing was then applied to analyze the molecular profiles of NAA25−deficient cells, and compared to the control group, NAA25 knockdown could activate apoptosis-related pathways, reduce the activation of tumor-associated signaling pathways and decrease immune response-associated pathways. Additionally, RT-qPCR was employed to validate these results. Taken together, our results revealed that NAA25 was highly expressed in breast cancer, and NAA25 knockdown might serve as a therapeutic target in breast cancer.

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The relationship between the prognosis of children with acute arterial stroke and polymorphisms of CDKN2B, HDAC9, NINJ2, NAA25 genes

Cited by 5 publications

References 37 publications

ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome‐wide DNA methylation pilot study

ZNF718, HOXA4, and ZFP57 are differentially methylated in periodontitis in comparison with periodontal health: Epigenome‐wide DNA methylation pilot study

Association of DNA Methylation in Blood Pressure-Related Genes With Ischemic Stroke Risk and Prognosis

Knockdown of NAA25 Suppresses Breast Cancer Progression by Regulating Apoptosis and Cell Cycle

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