Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis

Zhu, Ziyu; Hou, Lifang; Bollati, Valentina; Tarantini, Letizia; Marinelli, Barbara; Cantone, Laura; Yang, Allen S.; Vokonas, Pantel; Lissowska, Jolanta; Fustinoni, Silvia; Pesatori, Angela Cecilia; Bonzini, Matteo; Apostoli, Pietro; Costa, Giovanni; Bertazzi, Pier Alberto; Chow, Wong Ho; Schwartz, Joel; Baccarelli, Andrea

doi:10.1093/ije/dyq154

Cited by 189 publications

(233 citation statements)

References 62 publications

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“…[17][18][19] Genome-wide DNA methylation (e.g., measured in repetitive sequences including, Alu, Sat2, and LINE-1) in white blood cells (WBCs) has been shown to be associated with age, gender, race, alcohol exposure, and family history of breast cancer. [20][21][22][23][24] Additionally, compared to histologically normal or normal-appearing tissues (adjacent to breast tumors), tumor tissues consistently have lower levels of DNA methylation (i.e., increased hypomethylation throughout the genome), even early in breast carcinogenesis. 4,5,25 Furthermore, there are reports of significant associations between LINE-1 methylation and breast tumor clinicopathological features, 3 as well as breast cancer prognosis.…”

Section: Introductionmentioning

confidence: 99%

Associations between genetic variation in one-carbon metabolism and LINE-1 DNA methylation in histologically normal breast tissues

Llanos

Marian²,

Brasky

et al. 2015

Epigenetics

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Genome-wide DNA hypomethylation is an early event in the carcinogenic process. Percent methylation of long interspersed nucleotide element-1 (LINE-1) is a biomarker of genome-wide methylation and is a potential biomarker for breast cancer. Understanding factors associated with percent LINE-1 DNA methylation in histologically normal tissues could provide insight into early stages of carcinogenesis. In a cross-sectional study of 121 healthy women with no prior history of cancer who underwent reduction mammoplasty, we examined associations between plasma and breast folate, genetic variation in one-carbon metabolism, and percent LINE-1 methylation using multivariable regression models (adjusting for race, oral contraceptive use, and alcohol use). Results are expressed as the ratio of LINE-1 methylation relative to that of the referent group, with the corresponding 95% confidence intervals (CI). We found no significant associations between plasma or breast folate and percent LINE-1 methylation. Variation in MTHFR, MTR, and MTRR were significantly associated with percent LINE-1 methylation. Variant allele carriers of MTHFR A1289C had 4% lower LINE-1 methylation (Ratio 0.96, 95% CI 0.93-0.98), while variant allele carriers of MTR A2756G (Ratio 1.03, 95% CI 1.01-1.06) and MTRR A66G (Ratio 1.03, 95% CI 1.01-1.06) had 3% higher LINE-1 methylation, compared to those carrying the more common genotypes of these SNPs. DNA methylation of LINE-1 elements in histologically normal breast tissues is influenced by polymorphisms in genes in the one-carbon metabolism pathway. Future studies are needed to investigate the sociodemographic, environmental and additional genetic determinants of DNA methylation in breast tissues and the impact on breast cancer susceptibility.

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Section: Introductionmentioning

confidence: 99%

Associations between genetic variation in one-carbon metabolism and LINE-1 DNA methylation in histologically normal breast tissues

Llanos

Marian²,

Brasky

et al. 2015

Epigenetics

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“…In the analysis, we controlled for the following covariates a priori based on the relevant literature: 6,19,26,27 total PM 2.5 mass, cell proportions (CD4 C T lymphocytes, CD8 C T lymphocytes, natural killer cells, B cells, monocytes) estimated by the Houseman et al method, [28][29][30] age, body mass index [BMI, computed as weight (in kilograms) divided by height (in square meters)], cigarette pack years, smoking status (never, ever), alcohol consumption ( 2 drinks/day, < 2 drinks/day), years of education, year and season (spring: March-May, summer: June-August, fall: September-November, winter: December-February). Potential batch effects were also considered, including plate, the position of the chip on plate, and the row and column position on the chip.…”

Section: Discussionmentioning

confidence: 99%

Differential DNA methylation and PM_2.5 species in a 450K epigenome-wide association study

et al. 2017

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Although there is growing evidence that exposure to ambient particulate matter is associated with global DNA methylation and gene-specific methylation, little is known regarding epigenome-wide changes in DNA methylation in relation to particles and, especially, particle components. Using the Illumina Infinium HumanMethylation450 BeadChip, we examined the relationship between one-year moving averages of PM 2.5 species (Al, Ca, Cu, Fe, K, Na, Ni, S, Si, V, and Zn) and DNA methylation at 484,613 CpG probes in a longitudinal cohort that included 646 subjects. Bonferroni correction was applied to adjust for multiple comparisons. Bioinformatics analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was also performed. We observed 20 Bonferroni significant (P-value < 9.4£ 10 ¡9 ) CpGs for Fe, 8 for Ni, and 1 for V. Particularly, methylation at Schlafen Family Member 11 (SLFN11) cg10911913 was positively associated with measured levels of all 3 species. The SLFN11 gene codes for an interferoninduced protein that inhibits retroviruses and sensitizes cancer cells to DNA-damaging agents. Bioinformatics analysis suggests that gene targets may be relevant to pathways including cancers, signal transduction, and cell growth and death. Ours is the first study to examine the epigenome-wide association between ambient particles species and DNA methylation. We found that long-term exposures to specific components of ambient particle pollution, especially particles emitted during oil combustion, were associated with methylation changes in genes relevant to immune responses. Our findings provide insight into potential biologic mechanisms on an epigenetic level.

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“…The main weakness is that the differences found are small. Recently, several studies 13,31 have evaluated the association between levels of LINE-1 methylation and different characteristics of healthy subjects in blood DNA. The significantly differences found were also within the range of values of our study.…”

Section: Discussionmentioning

confidence: 99%

Type 2 diabetes mellitus in relation to global LINE-1 DNA methylation in peripheral blood: A cohort study

et al. 2014

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In the last years, epigenetic processes have emerged as a promising area of complex diseases research. DNA methylation measured in Long Interspersed Nucleotide Element 1 (LINE-1) sequences has been considered a surrogate marker for global genome methylation. New findings have suggested the potential involvement of epigenetic mechanisms in Type 2 diabetes (T2DM) as a crucial interface between the effects of genetic predisposition and environmental influences. Our study evaluated whether global DNA methylation predicted increased risk from T2DM or other carbohydrate metabolism disorders in a cohort study. We used a prospective cohort intervention study and a control group. We collected phenotypic, anthropometric, biochemical, and nutritional information from all subjects. Global LINE-1 DNA methylation was quantified by pyrosequencing technology. Subjects that did not improve their carbohydrate metabolism status showed lower levels of global LINE-1 DNA methylation (63.9 § 1.7 vs. 64.7 § 2.4) and they practiced less intense physical activity (5.8% vs. 21.5%). Logistic regression analyses showed a significant association between LINE-1 DNA methylation and metabolic status after adjustment for sex, age, BMI, and physical activity. Our study showed that lower LINE-1 DNA methylation levels were associated with a higher risk metabolic status worsening, independent of other classic risk factors. This finding highlights the potential role for epigenetic biomarkers as predictors of T2DM risk or other related metabolic disorders.

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Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis

Cited by 189 publications

References 62 publications

Associations between genetic variation in one-carbon metabolism and LINE-1 DNA methylation in histologically normal breast tissues

Associations between genetic variation in one-carbon metabolism and LINE-1 DNA methylation in histologically normal breast tissues

Differential DNA methylation and PM_2.5 species in a 450K epigenome-wide association study

Type 2 diabetes mellitus in relation to global LINE-1 DNA methylation in peripheral blood: A cohort study

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Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis

Cited by 189 publications

References 62 publications

Associations between genetic variation in one-carbon metabolism and LINE-1 DNA methylation in histologically normal breast tissues

Associations between genetic variation in one-carbon metabolism and LINE-1 DNA methylation in histologically normal breast tissues

Differential DNA methylation and PM2.5 species in a 450K epigenome-wide association study

Type 2 diabetes mellitus in relation to global LINE-1 DNA methylation in peripheral blood: A cohort study

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Differential DNA methylation and PM_2.5 species in a 450K epigenome-wide association study