<i>LINE-1</i> and inflammatory gene methylation levels are early biomarkers of metabolic changes: association with adiposity

Carraro, Júlia Cristina Cardoso; Mansego, María Luisa; Milagro, Fermı́n I.; Chaves, Larissa Oliveira; Vidigal, Fernanda Carvalho; Bressan, Josefina; Martínéz, J. Alfredo

doi:10.3109/1354750x.2016.1171904

Cited by 23 publications

(14 citation statements)

References 56 publications

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“…Because of its high representation throughout the genome, LINE-1 methylation has been shown to correlate with global genomic DNA methylation content [50], and is regarded as a measure of global DNA methylation [51]. Some investigations have linked changes in LINE-1 methylation to inflammation [52,53]. Lower LINE-1 methylation was associated with higher serum vascular Cell Adhesion Molecule-1 [54], which has been identified as an independent marker of cardiovascular disease [55].…”

Section: Discussionmentioning

confidence: 99%

Long-term ambient fine particulate matter and DNA methylation in inflammation pathways: results from the Sister Study

Wang

O’Brien

et al. 2019

Epigenetics

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Although underlying mechanisms of long-term exposure to air pollution and cardiovascular disease remain obscure, effects might partially act through changes in DNA methylation. We examined the associations between long-term ambient fine particulate matter (PM 2.5 ) and methylation, considering both a global measure and methylation at several specific inflammation-related loci, in two random subcohorts selected from a nationwide prospective study of US women. In one sub-cohort we measured long interspersed nucleotide element (LINE-1); in the other, we measured methylation at three candidates CpG loci related to inflammatory pathways [tumour necrosis factor-alpha (TNF-α) and toll-like receptor-2 (TLR-2)]. Annual average contemporaneous ambient PM 2.5 concentrations were estimated for the current residence. We used both classical least-squares and quantile regression models to estimate the long-term effects. The women in sub-cohorts 1 (n = 491) and 2 (n = 882) had mean ages of 55.8 and 56.7, respectively. Neither modelling approach showed an association between long-term PM 2.5 and LINE-1 methylation or between PM 2.5 and either of the two CpG sites in TLR-2. Using linear regression, there was an estimated change of −6.5% (95% confidence interval CI: −13.34%, 0.35%) in mean methylation of TNF-α per 5 µg/m 3 increase in PM 2.5 . Quantile regression showed that the downward shift was mainly in the lower half of the distribution of DNA methylation. Long-term residence in regions with higher ambient PM 2.5 may be associated with increased TNF-α through a reduction in methylation, particularly in the lower tail. Epigenetic markers and quantile regression might provide insight into mechanisms underlying the relationship between air pollution and cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

Long-term ambient fine particulate matter and DNA methylation in inflammation pathways: results from the Sister Study

Wang

O’Brien

et al. 2019

Epigenetics

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“…Moreover, the subjects in the Samoan study had a substantially higher BMI than our study subjects and the NTFS study subjects. Recent reports indicate that alterations in DNA methylation are closely associated with obesity 24 , 25 ) . The Multi-Ethnic Study of Atherosclerosis (MESA) reported that individuals with high BMI (≥ 40 kg/m 2 ) had higher LINE-1 DNA methylation levels in leukocytes than those with normal BMI (< 25 kg/m 2 ) in a cohort of 987 individuals aged 45–84 years 26 ) .…”

Section: Discussionmentioning

confidence: 99%

Relationship between Long Interspersed Nuclear Element-1 DNA Methylation in Leukocytes and Dyslipidemia in the Japanese General Population

Tsuboi

Yamada

Munetsuna

et al. 2018

J Atheroscler Thromb

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Aim: Aberrant global DNA methylation is involved in the development of several diseases, including cardiovascular disease (CVD). We investigated whether the methylation of long interspersed nuclear element-1 (LINE-1) in leukocytes is associated with dyslipidemia, a major risk factor for CVD, in the Japanese general population.Methods: We conducted a cross-sectional study consisting of 420 Japanese subjects (187 men and 233 women) without a clinical history of cancer, stroke, or ischemic heart disease. LINE-1 DNA methylation levels in leukocytes were measured using a pyrosequencing method.Results: Significantly higher odds ratios (ORs) for hypermethylation were observed in the high LDL cholesterol and high LDL/HDL ratio groups than the corresponding normal group (high LDLC group: OR, 1.88; 95% confidence interval [CI], 1.20–2.96, high LDL/HDL ratio group: OR, 1.90; 95% CI, 1.20–3.01). Subjects with 2 or more lipid abnormalities had significantly higher ORs for hypermethylation than those with no lipid abnormality (OR, 2.31; 95% CI, 1.11–4.82).Conclusion: LINE-1 DNA hypermethylation in leukocytes was associated with CVD risk profiles: high LDLC, high LDL/HDL ratio, and the degree of abnormal lipid metabolism.Abbreviations:ANOVA, analysis of variance; BMI, body mass index; CI, confidence interval; CRP, C-reactive protein; CVD, cardiovascular disease; DNMT, DNA methyltransferase; EDTA, ethylenediaminetetraacetic acid; HDLC, high-density lipoprotein cholesterol; IL-6, interleukin-6; KLF2, Krüppel-like factor 2; LDLC, low-density lipoprotein cholesterol; LINE-1, long interspersed nuclear element-1; OR, odds ratio; PCR, polymerase chain reaction; SD, standard deviation; TC, total cholesterol; TG, triglyceride;

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“…Global and gene-specific DNA methylation alterations, which vary with age, sex and socioeconomic status, may also be predictive biomarkers of weight loss response to intervention programs ( 91 ). Global DNA methylation and inflammatory gene promoter hypermethylation are reported to be early biomarkers of adiposity and metabolic alterations ( 93 ). Global DNA methylation and hydroxymethylation may functions as biomarkers in obesity and associated comorbidities.…”

Section: Discussionmentioning

confidence: 99%

INSIG2 rs7566605 single nucleotide variant and global DNA methylation index levels are associated with weight loss in a personalized weight reduction program

et al. 2017

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Single nucleotide polymorphisms associated with lipid metabolism and energy balance are implicated in the weight loss response caused by nutritional interventions. Diet-induced weight loss is also associated with differential global DNA methylation. DNA methylation has been proposed as a predictive biomarker for weight loss response. Personalized biomarkers for successful weight loss may inform clinical decisions when deciding between behavioral and surgical weight loss interventions. The aim of the present study was to investigate the association between global DNA methylation, genetic variants associated with energy balance and lipid metabolism, and weight loss following a non-surgical weight loss regimen. The present study included 105 obese participants that were enrolled in a personalized weight loss program based on their allelic composition of the following five energy balance and lipid metabolism-associated loci: Near insulin-induced gene 2 (INSIG2); melanocortin 4 receptor; adrenoceptor β2; apolipoprotein A5; and G-protein subunit β3. The present study investigated the association between a global DNA methylation index (GDMI), the allelic composition of the five energy balance and lipid metabolism-associated loci, and weight loss during a 12 month program, after controlling for age, sex and body mass index (BMI). The results demonstrated a significant association between the GDMI and near INSIG2 locus, after adjusting for BMI and weight loss, and significant trends were observed when stratifying by gender. In conclusion, a combination of genetic and epigenetic biomarkers may be used to design personalized weight loss interventions, enabling adherence and ensuring improved outcomes for obesity treatment programs. Precision weight loss programs designed based on molecular information may enable the creation of personalized interventions for patients, that use genomic biomarkers for treatment design and for treatment adherence monitoring, thus improving response to treatment.

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LINE-1 and inflammatory gene methylation levels are early biomarkers of metabolic changes: association with adiposity

Cited by 23 publications

References 56 publications

Long-term ambient fine particulate matter and DNA methylation in inflammation pathways: results from the Sister Study

Long-term ambient fine particulate matter and DNA methylation in inflammation pathways: results from the Sister Study

Relationship between Long Interspersed Nuclear Element-1 DNA Methylation in Leukocytes and Dyslipidemia in the Japanese General Population

INSIG2 rs7566605 single nucleotide variant and global DNA methylation index levels are associated with weight loss in a personalized weight reduction program

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