Analysis of DNA methylation of potential age-related methylation sites in canine peripheral blood leukocytes

Pregnancy is a valuable model to study the association between DNA methylation and several cardiometabolic traits, due to its direct potential to influence mother’s and child’s health. Epigenetics in Pregnancy (EPIPREG) is a population-based sample with the aim to study associations between DNA-methylation in pregnancy and cardiometabolic traits in South Asian and European pregnant women and their offspring. This cohort profile paper aims to present our sample with genetic and epigenetic data and invite researchers with similar cohorts to collaborative projects, such as replication of ours or their results and meta-analysis. In EPIPREG we have quantified epigenome-wide DNA methylation in maternal peripheral blood leukocytes in gestational week 28±1 in Europeans (n = 312) and South Asians (n = 168) that participated in the population-based cohort STORK Groruddalen, in Norway. DNA methylation was measured with Infinium MethylationEPIC BeadChip (850k sites), with technical validation of four CpG sites using bisulphite pyrosequencing in a subset (n = 30). The sample is well characterized with few missing data on e.g. genotype, universal screening for gestational diabetes, objectively measured physical activity, bioelectrical impedance, anthropometrics, biochemical measurements, and a biobank with maternal serum and plasma, urine, placenta tissue. In the offspring, we have repeated ultrasounds during pregnancy, cord blood, and anthropometrics up to 4 years of age. We have quantified DNA methylation in peripheral blood leukocytes in nearly all eligible women from the STORK Groruddalen study, to minimize the risk of selection bias. Genetic principal components distinctly separated Europeans and South Asian women, which fully corresponded with the self-reported ethnicity. Technical validation of 4 CpG sites from the methylation bead chip showed good agreement with bisulfite pyrosequencing. We plan to study associations between DNA methylation and cardiometabolic traits and outcomes.

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DNA Methylation-Based Age Prediction and Telomere Length Reveal an Accelerated Aging in Induced Sputum Cells Compared to Blood Leukocytes: A Pilot Study in COPD Patients

Frontiers in Medicine ◽

10.3389/fmed.2021.690312 ◽

2021 ◽

Vol 8 ◽

Author(s):

Manuela Campisi ◽

Filippo Liviero ◽

Piero Maestrelli ◽

Gabriella Guarnieri ◽

Sofia Pavanello

Keyword(s):

Dna Methylation ◽

Telomere Length ◽

Peripheral Blood ◽

Induced Sputum ◽

Biological Aging ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes ◽

Copd Patients ◽

New Findings ◽

Age Prediction

Aging is the predominant risk factor for most degenerative diseases, including chronic obstructive pulmonary disease (COPD). This process is however very heterogeneous. Defining the biological aging of individual tissues may contribute to better assess this risky process. In this study, we examined the biological age of induced sputum (IS) cells, and peripheral blood leukocytes in the same subject, and compared these to assess whether biological aging of blood leukocytes mirrors that of IS cells. Biological aging was assessed in 18 COPD patients (72.4 ± 7.7 years; 50% males). We explored mitotic and non-mitotic aging pathways, using telomere length (TL) and DNA methylation-based age prediction (DNAmAge) and age acceleration (AgeAcc) (i.e., difference between DNAmAge and chronological age). Data on demographics, life style and occupational exposure, lung function, and clinical and blood parameters were collected. DNAmAge (67.4 ± 5.80 vs. 61.6 ± 5.40 years; p = 0.0003), AgeAcc (−4.5 ± 5.02 vs. −10.8 ± 3.50 years; p = 0.0003), and TL attrition (1.05 ± 0.35 vs. 1.48 ± 0.21 T/S; p = 0.0341) are higher in IS cells than in blood leukocytes in the same patients. Blood leukocytes DNAmAge (r = 0.927245; p = 0.0026) and AgeAcc (r = 0.916445; p = 0.0037), but not TL, highly correlate with that of IS cells. Multiple regression analysis shows that both blood leukocytes DNAmAge and AgeAcc decrease (i.e., younger) in patients with FEV1% enhancement (p = 0.0254 and p = 0.0296) and combined inhaled corticosteroid (ICS) therapy (p = 0.0494 and p = 0.0553). In conclusion, new findings from our work reveal a differential aging in the context of COPD, by a direct quantitative comparison of cell aging in the airway with that in the more accessible peripheral blood leukocytes, providing additional knowledge which could offer a potential translation into the disease management.

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Quantification of Global DNA Methylation in Canine Melanotic and Amelanotic Oral Mucosal Melanomas and Peripheral Blood Leukocytes From the Same Patients With OMM: First Study

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.680181 ◽

2021 ◽

Vol 8 ◽

Author(s):

Nayra Villar Scattone ◽

Tatiane Moreno Ferrarias Epiphanio ◽

Karine Germano Caddrobi ◽

Juliana Shimara Pires Ferrão ◽

Francisco Javier Hernandez-Blazquez ◽

...

Keyword(s):

Dna Methylation ◽

Peripheral Blood ◽

High Performance ◽

Global Dna Methylation ◽

Image Analysis System ◽

Peripheral Blood Leukocytes ◽

Dna Hypomethylation ◽

Blood Leukocytes ◽

Tissue Samples ◽

Analysis System

Oral mucosal melanomas (OMMs) are aggressive and resistant cancers of high importance in veterinary oncology. Amelanotic OMM produces comparatively less melanin and is considered to be more aggressive than melanotic OMM. Global DNA methylation profiles with hypomethylated or hypermethylated patterns have both been associated with aggressive neoplasms; however, global DNA hypomethylation seems to correlate to higher aggressiveness. Accordingly, global DNA methylation in peripheral blood leukocytes has been investigated to understand the role of systemic or environmental factors in cancer development. This study aimed to quantify global DNA methylation in canine melanotic and amelanotic OMM samples and in the peripheral blood leukocytes of the same dogs. Tumor tissue samples were collected from 38 dogs, of which 19 were melanotic and 19 were amelanotic OMM. These were submitted to immunohistochemistry (IHC) with anti-5-methylcytosine (5mC) and anti-Ki67 primary antibodies. Ki67- and 5mC-positive nuclei were manually scored with the help of an image analysis system. Peripheral blood samples were collected from 18 among the 38 OMM-bearing dogs and from 7 additional healthy control dogs. Peripheral blood leukocytes were isolated from the 25 dogs, and DNA was extracted and analyzed by high-performance liquid chromatography (HPLC) for global DNA methylation. The pattern of global DNA methylation in both canine melanotic and amelanotic OMM indicated higher percentages of weakly or negatively stained nuclei in most of the OMM cells, presuming predominant global DNA hypomethylation. In addition, Ki67 counts in amelanotic OMM were significantly higher than those in melanotic OMM (p < 0.001). Global DNA methylation different immunostaining patterns (strong, weak or negative) correlated with Ki67 scores. Global DNA methylation in circulating leukocytes did not differ between the 9 melanotic and 9 amelanotic OMM or between the 18 OMM-bearing dogs and the 7 healthy dogs. This study provides new information on canine melanotic and amelanotic OMM based on global DNA methylation and cell proliferation.

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Abstract 834: Epigenome-wide profiling of DNA methylation in peripheral blood leukocytes and the prognosis of prostate cancer patients in African Americans

10.1158/1538-7445.am2019-834 ◽

2019 ◽

Author(s):

Junfeng Xu ◽

Chia-Wen Tsai ◽

Wen-Shin Chang ◽

Da-Tian Bau ◽

Jian Gu

Keyword(s):

Prostate Cancer ◽

Dna Methylation ◽

African Americans ◽

Cancer Patients ◽

Peripheral Blood ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes

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SOAT1 methylation is associated with coronary heart disease

Lipids in Health and Disease ◽

10.1186/s12944-019-1138-9 ◽

2019 ◽

Vol 18 (1) ◽

Author(s):

Jialin Abuzhalihan ◽

Yong-Tao Wang ◽

Yi-Tong Ma ◽

Zhen-Yan Fu ◽

Yi-Ning Yang ◽

...

Keyword(s):

Dna Methylation ◽

Coronary Heart Disease ◽

Heart Disease ◽

Candidate Genes ◽

Peripheral Blood ◽

Cholesterol Absorption ◽

Peripheral Blood Leukocytes ◽

Promoter Regions ◽

Blood Leukocytes ◽

Cpg Sites

Abstract Background This study was designed to investigate whether differential DNA methylationin of cholesterol absorption candidate genes can function as a biomarker for patients with coronary heart disease (CHD). Methods DNA methylation levels of the candidate genes FLOT1, FLOT2 and SOAT1 were measured in peripheral blood leukocytes (PBLs) from 99 patients diagnosed with CHD and 89 control subjects without CHD. A total of 110 CPG sites around promoter regions of them were examined. Results Compared with groups without CHD, patients with CHD had lower methylation levels of SOAT1 (P<0.001). When each candidate genes were divided into different target segments, patients with CHD also had lower methylation levels of SOAT1 than patients without (P = 0.005). After adjustment of other confounders, methylation levels of SOAT1 were still associated with CHD (P = 0.001, OR = 0.290, 95% CI: 0.150–0.561). Conclusions SOAT1 methylation may be associated with development of CHD. Patients with lower methylation levels in SOAT1 may have increased risks for CHD. Further studies on the specific mechanisms of this relationship are necessary.

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Hypomethylation of the IL17RC Promoter in Peripheral Blood Leukocytes Is Not A Hallmark of Age-Related Macular Degeneration

Cell Reports ◽

10.1016/j.celrep.2013.11.042 ◽

2013 ◽

Vol 5 (6) ◽

pp. 1527-1535 ◽

Cited By ~ 25

Author(s):

Verity F. Oliver ◽

Maria Franchina ◽

Andrew E. Jaffe ◽

Kari E. Branham ◽

Mohammad Othman ◽

...

Keyword(s):

Macular Degeneration ◽

Peripheral Blood ◽

Age Related Macular Degeneration ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes ◽

Age Related

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Cohort Profile: Epigenetics in Pregnancy (EPIPREG) – population-based sample of European and South Asian pregnant women living in Norway with epigenome-wide DNA methylation (850k) in peripheral blood leukocytes

10.1101/2021.02.08.21251341 ◽

2021 ◽

Author(s):

Nicolas Fragoso-Bargas ◽

Julia O. Opsahl ◽

Nadezhda Kiryushchenko ◽

Yvonne Böttcher ◽

Sindre Lee-Ødegård ◽

...

Keyword(s):

Dna Methylation ◽

South Asian ◽

Peripheral Blood ◽

Meta Analysis ◽

Population Based ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes ◽

Wide Range ◽

Cardiometabolic Traits ◽

In Pregnancy

ABSTRACTPurposePregnancy is a valuable model to study the association between DNA methylation and several cardiometabolic traits, due to its direct potential to influence mother’s and child’s health. Epigenetics in Pregnancy (EPIPREG) is a population-based sample with the aim to study associations between DNA-methylation in pregnancy and cardiometabolic traits in South Asian and European pregnant women and their offspring.ParticipantsIn EPIPREG we have quantified epigenome-wide DNA methylation in maternal peripheral blood leukocytes in gestational week 28±1 in Europeans (n=312) and South Asians (n=168) that participated in the population-based cohort STORK Groruddalen, in Norway. DNA methylation was measured with Infinium MethylationEPIC Kit (850k sites), with technical validation of four CpG sites using bisulphite pyrosequencing in a subset (n=30). The sample is well characterized with few missing data on e.g. genotype, universal screening for gestational diabetes, objectively measured physical activity, bioelectrical impedance, anthropometrics, biochemical measurements, and a biobank with maternal serum and plasma, urine, placenta tissue. In offspring, we have repeated ultrasounds during pregnancy, cord blood, and anthropometrics up to 4 years of age.Results to dateWe have quantified DNA methylation in peripheral blood leukocytes in nearly all eligible women from the STORK Groruddalen study, to minimize the risk of selection bias. Genetic principal components distinctly separated Europeans and South Asian women, which fully corresponded with the self-reported ethnicity. Technical validation of 4 CpG sites from the methylation bead chip showed high concordance with bisulfite pyrosequencing (R=0.98, p<0.001).Future plansWe plan to study associations between DNA methylation and cardiometabolic traits and outcomes. We hope to identify cohorts with similar data to replicate our findings, collaborate on joint efforts such as meta-analysis, and serve as a replication cohort for other studies.Strengths and limitations of this study-Epigenome-wide DNA methylation data in maternal peripheral blood leukocytes in gestational week 28±1 in 312 Europeans and 168 South Asians living in Norway-EPIPREG’s population-based design and comprehensive phenotyping allows for studies of a wide range of phenotypic traits, exposures and outcomes in relation to DNA methylation-The inclusion of women with both European and South Asian ethnic background enables interesting studies into the role of DNA methylation in ethnic disparities in health.-The wide range of collected phenotypes, exposures and outcomes makes the EPIPREG sample well suited to serve as a replication cohort for other cohorts with DNA methylation data-The EPIPREG sample has limited statistical power for epigenome-wide association studies, and we are interested in collaborative efforts such as meta-analysis of several cohorts

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