Abstract P251: Epigenome-Wide Study of Erythrocyte Fatty Acids in the Genetics of Lipid Lowering Drugs and Diet Network

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Stella Aslibekyan ◽  
Bertha Hidalgo ◽  
Marguerite M Irvin ◽  
Jin Sha ◽  
Hemant K Tiwari ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Fatty Acids ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Trans Fatty Acids ◽  
Saturated Fatty Acids ◽  
Methylation Status ◽  
Lipid Lowering ◽  
Cpg Sites ◽  
Cpg Site

Introduction: Dietary fatty acids have a role in many physiological mechanisms that influence cardiovascular health. An emerging body of evidence suggests that dietary fats may interact with genetic variants in regulating tissue levels of fatty acids, thus impacting disease risk. Epigenetic changes such as DNA methylation are a promising mechanism underlying such interactions. However, no studies to date have investigated the relationship between DNA methylation and tissue fatty acids at the genome-wide level. Methods: We have performed the first epigenome-wide association study (EWAS) of erythrocyte concentrations of polyunsaturated, monounsaturated, saturated, and trans fatty acids in 958 participants of the Genetics of Diet and Lipid Lowering Drugs Network (GOLDN). We assayed the methylation status of approximately 450,000 CpG sites in CD4+ T-cells. To investigate the associations between methylation of each CpG site and red blood cell fatty acids, we fit linear mixed models adjusted for age, sex, cell purity, and family structure. Results: The strongest association was observed between the methylation status of a CpG site in PDE4D, previously linked to systemic inflammation and stroke, and red blood cell trans fatty acids (P=4x10-7). In the analysis of polyunsaturated fatty acids, we found inverse associations with the methylation status of two CpG sites in BRSK2 (P=9x10-6 and P=1x10-5 respectively), as well as with a CpG site located in a “gene desert” on chromosome 14 proximally to VRK1 (P=5x10-7). BRSK2 encodes a kinase previously shown to control epigenetic programs that determine T-cell function. The top hits for monounsaturated and saturated fatty acids were located in ATL2 (P=1x10-6) and FGD2 (P=1x10-5), respectively. Conclusions: We present preliminary evidence of cross-sectional association between the methylation status of several biologically relevant genomic regions and erythrocyte concentrations of polyunsaturated, trans, monounsaturated, and saturated fatty acids. Upon successful validation, these findings further current understanding of gene-fatty acid interactions in human health and disease.

scholarly journals Six‐Year Change in Red Blood Cell Omega‐3 and Trans Fatty Acids in the Framingham Heart Study

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
William S Harris ◽  
James V Pottala ◽  
Ramachandran S Vasan ◽  
Martin G Larson ◽  
Sander J Robins
Keyword(s):  
Fatty Acids ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Framingham Heart Study ◽  
Trans Fatty Acids ◽  
Omega 3 ◽  
Heart Study

Telomere Length in Healthy Adults Is Positively Associated With Polyunsaturated Fatty Acids, Including Arachidonic Acid, and Negatively With Saturated Fatty Acids

2020 ◽  
Vol 76 (1) ◽  
pp. 3-6
Author(s):  
Varinderpal S Dhillon ◽  
Permal Deo ◽  
Ann Chua ◽  
Phil Thomas ◽  
Michael Fenech
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Fatty Acid ◽  
Blood Cell ◽  
Telomere Length ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Saturated Fatty Acids ◽  
Fatty Acid Status ◽  
Acid Status

Abstract Lymphocyte telomere length (LTL) is a biomarker of aging that may be modified by dietary factors including fat. Red blood cell fatty acid status is a well-validated indicator of long-term dietary intake of fat from various sources. Recent findings from epidemiological studies of LTL in relation to fatty acids in red blood cells are not conclusive. The present study was carried out to investigate if red blood cell fatty acid status in 174 healthy older South Australians is associated with LTL. Lymphocyte telomere length was measured by real-time qPCR and fatty acid content in red blood cells was measured by gas chromatography. Our results indicate that the majority of saturated fatty acids and monounsaturated fatty acids are negatively associated with LTL, whereas polyunsaturated fatty acids are positively associated with LTL. Multiple regression analysis revealed that arachidonic acid (C20:4n-6) is significantly, independently, positively correlated with LTL (β = 0.262; p = .000). The significant association of fatty acids, particularly C20:4n-6, with telomere length warrants further research.

Abstract 25: Epigenome-Wide DNA Methylation Analysis Reveals Novel Hematologic Trait Associations for African Americans in The Jackson Heart Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Mindy D Szeto ◽  
Laura M Raffield ◽  
Deborah A Nickerson ◽  
Neil A Zakai ◽  
Dwight J Klemm ◽  
...  
Keyword(s):  
Dna Methylation ◽  
African Americans ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Mean Corpuscular Hemoglobin ◽  
Red Cell ◽  
Corpuscular Hemoglobin ◽  
Cpg Sites ◽  
Heart Study ◽  
Trait Associations

Cardiovascular disease (CVD) is the leading cause of death in the U.S. and disproportionately affects African Americans (AAs). Routinely measured circulating red blood cell traits, which are highly heritable and differ by ethnicity, are independent predictors for CVD-related traits including hypertension, stroke, coronary heart disease, and CVD mortality. Many genetic loci associated with red blood cell count (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW) have been identified. However, identified genetic variants do not fully explain the heritability of these traits. Epigenetic alterations in DNA methylation likely also explain a portion of red cell trait variance, and detecting methylation quantitative trait loci (meQTLs) can provide critical insight into the development of CVD and CVD health disparities. We performed an epigenome-wide association analysis to identify CpG sites at which DNA methylation levels are associated with red blood cell traits in 1753 participants from the Jackson Heart Study, a population-based cohort of AAs. DNA methylation was measured by the Illumina MethylationEPIC array, interrogating approximately 850,000 CpG sites in peripheral blood mononuclear cells at the baseline exam. Associations were assessed using linear mixed models adjusted for age, sex, cell proportions, genetic ancestry, and experimental batch effects. A Bonferroni-corrected p-value of 9x10 -8 was used to assess statistical significance. We identified many significant differentially methylated CpG sites associated with red blood cell traits. Analysis of RBC, HGB, MCV, MCH, and MCHC revealed a novel highly significant association with a CpG annotated to a non-coding RNA (cg11703701; RBC P = 5.19x10 -22 , HGB P = 1.19x10 -11 , MCV P = 4.69x10 -59 , MCH P = 2.68x10 -67 , MCHC P = 2.32x10 -31 ), as well as a strong signal for a reprogramming-specific differentially methylated region (cg04321267; RBC P = 1.67x10 -16 , HGB P = 3.58x10 -12 , MCV P = 2.12x10 -49 , MCH P = 1.74x10 -57 , MCHC P = 5.91x10 -30 ). Multiple CpGs annotated to genes HBA1 and HBA2 were associated with RBC, MCV, MCH, and MCHC, while ITPKB (cg23740281; HGB P = 4.88x10 -10 , HCT P = 6.20x10 -11 ) and ALDH2 (cg17969951; HGB P = 3.03x10 -11 , HCT P = 8.31x10 -9 ) were significantly associated with both HGB and HCT. Additional CpG sites were significantly associated with HCT ( PLXND1 cg22902177; P = 7.54x10 -11 and ARL1 cg23903357; P = 9.86x10 -11 ) and RDW ( CPNE2 cg09018739; P = 3.03x10 -22 ). These findings shed light on potential hematologic and CVD mechanisms in understudied populations. Future work will explore the role of neighboring SNPs in mediating observed methylation-trait associations, and replicate results in an additional multi-ethnic cohort.

The proportion of total C18:1 trans -fatty acids in red blood cell membranes relates to carotid plaque prevalence

2016 ◽  
Vol 38 ◽  
pp. 81-85
Author(s):  
Zoe Herreras ◽  
Montserrat Cofán ◽  
Marta Catalan ◽  
Carlos Calvo ◽  
Montserrat Pinyol ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Carotid Plaque ◽  
Trans Fatty Acids ◽  
Cell Membranes ◽  
Red Blood Cell Membranes

scholarly journals Red Blood Cell Membrane Fatty Acids in U. S. Blood Donors (P06-123-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Carissa Powers ◽  
David Scully ◽  
Rosemary Schleicher
Keyword(s):  
Gender Differences ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Blood Donors ◽  
Saturated Fatty Acids ◽  
Omega 3 ◽  
Cardiac Events ◽  
Membrane Fatty Acids

Abstract Objectives The purpose of this study was to use a newly validated method for measuring 21 cis-fatty acids in red blood cell (RBC) membranes to investigate race-ethnic and gender differences in saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA). In addition, two long-chain PUFA, namely, eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), were summed to provide an Omega-3 Index for each participant. This index is considered a cardiovascular risk factor. Methods Units (n = 120) of whole blood in EDTA were purchased from BioIVT (Westbury, NY). The demographic make-up of the set was 60:60 men: women. Of the 120 blood donors, 37% were black, 29% were white, and 34% were Hispanic. Average ages were 44 y (black), 48 y (white), and 43 y (Hispanic). Upon arrival, units were washed, treated with 1% BHT, and packed RBC were frozen until time of analysis. Hydrolysis of esters, derivitization with pentafluorobenzyl bromide, gas chromatography, and mass spectrometric detection were carried out to measure the 21 most abundant cis-fatty acid concentrations in RBC, which were converted to weight percentages of total. For the Omega-3 Index, the percentage of totals calculated for EPA and DHA were summed. Results There were few small (≤1%) race-ethnic differences and no gender differences in the proportions of fatty acids as SFA, MUFA, or PUFA; overall these averaged (SD) 44% (1%), 16% (1%), and 40% (1%), respectively. The Omega-3 Index averaged (SD) 3.5% (1%). One blood donor reached the suggested goal of ≥ 8%, which is associated with low risk for cardiac events. Conclusions This small study was undertaken in advance of the U.S. nationally representative survey, NHANES 2019–2020, in which RBC membrane fatty acids will be measured in the same laboratory. It will be interesting to learn whether NHANES will confirm the mostly null demographic findings in RBC fatty acid percentages and the low average Omega-3 Index. Funding Sources None.

scholarly journals Study on the relationship between DNA methylation of target CpG sites in peripheral blood and gestational diabetes during early pregnancy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaolei Wang ◽  
Jin Huang ◽  
Yixiang Zheng ◽  
Sisi Long ◽  
Huijun Lin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gestational Diabetes ◽  
Early Pregnancy ◽  
Roc Curve ◽  
Peripheral Blood ◽  
Methylation Status ◽  
First Trimester ◽  
Independent Effect ◽  
Cpg Sites ◽  
Cpg Site

AbstractGenome-wide DNA methylation profiling have been used to find maternal CpG sites related to the occurrence of gestational diabetes mellitus (GDM). However, none of these differential sites found has been verified in a larger sample. Here, our aim was to evaluate whether first trimester changes in target CpG sites in the peripheral blood of pregnancy women predict subsequent development of GDM. This nested case–control study was based upon an early pregnancy follow-up cohort (ChiCTR1900020652). Target CpG sites were extracted from related published literature and bioinformatics analysis. The DNA methylation levels at 337 CpG sites of 80 GDM cases and 80 matched healthy controls during the early pregnancy (10–15 weeks) were assessed using MethylTarget sequencing. The best cut-off level for methylation of CpG site was determined using the generated ROC curve. The independent effect of CpG site methylation status on GDM was analyzed using conditional logistic regression. Methylation levels at 6 CpG sites were significantly higher in the GDM group than in controls, whereas those at another 6 CpG sites were significantly lower (FDR < 0.05). The area under the ROC curve at each methylation level of the significant CpG sites ranged between 0.593 and 0.650 for the occurrence of GDM. After adjusting for possible confounders, the hypermethylation status of CpG site 68167324 (OR = 3.168, 1.038–9.666) and 24837915 (OR = 5.232, 1.659–16.506) was identified as more strongly associated with GDM; meanwhile, the hypermethylation of CpG site 157130156 (OR = 0.361, 0.135–0.966) and 89438648 (OR = 0.206, 0.065–0.655) might indicate lower risk of GDM. The methylation status of target CpG sites in the peripheral blood of pregnant women during the first trimester may be associated with GDM pathogenesis, and has potential as a predictor of GDM.

scholarly journals PSXI-32 Effects of algae DHA on fatty acid profile of plasma red blood cell membrane and fecal microbiota of adult cats

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 319-319
Author(s):  
Carrie James ◽  
Sandra L Rodriguez-Zas ◽  
Maria R C de Godoy
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Blood Cell ◽  
Fish Oil ◽  
Red Blood Cell ◽  
Fecal Microbiota ◽  
Fatty Acid Profiles ◽  
Male Adult ◽  
Poultry Fat ◽  
Adult Cats

Abstract There is evidence that algae can be a sustainable alternative of omega-3 polyunsaturated fatty acids (w-3 PUFA; DHA and EPA) in the diets of felines, but more information is needed to determine bioavailability of algal w-3 PUFAs in felines. Therefore, the objective of this study was to determine the effects of dietary supplementation of algae DHA on plasma and red blood cell (RBC) membrane fatty acid profiles and fecal microbiota of adult cats. A complete randomized design was utilized with thirty female and male adult cats (mean age: 1.8 ± 0.03 yr, mean BW: 4.5 ± 0.8 kg) which were fed an assigned diet for 90 d. Three diets were formulated with poultry fat alone or inclusion of 2% fish oil or 2% algae DHA meal. Blood samples were collected after fasting on 0, 30, 60 and 90 d to be analyzed for plasma and red blood cell fatty acid profiles. A fresh fecal sample was collected within 15 min of defecation from each cat to be analyzed for fecal microbiota. Illumina 16S rRNA sequencing from V4 region was completed using MiSeq and analyzed using QIIME 2. Plasma and RBC fatty acid concentrations at baseline were similar among all cats and treatment groups. However, dietary treatment had a significant effect on the concentrations of several fatty acids in plasma and RBC over time. Plasma and RBC concentrations of DHA were greater (P &lt; 0.05) for cats fed the algal DHA diet compared to the control and fish oil diets. Conversely, plasma and RBC concentrations of EPA did not differ among treatments when analyzed as a change from baseline. Beta- and alpha-diversity did not differ among treatments, indicating that 2% fish oil or algal-DHA meal does alter fecal microbiota of cats in contrast with cats fed a poultry fat-based diet.

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