Cardiovascular disease risk factors and DNA methylation at the<i>LINE-1</i>repeat region in peripheral blood from Samoan Islanders

Cash, Haley L; McGarvey, Stephen T.; Houseman, E. Andrés; Marsit, Carmen J.; Hawley, Nicola L.; Lambert-Messerlian, Geralyn; Viali, Satupaitea; Tuitele, John; Kelsey, Karl T.

doi:10.4161/epi.6.10.17728

Cited by 97 publications

(87 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We used quantitative bisulfite PCR pyrosequencing to measure LINE-1 DNA methylation (Cash et al, 2011; Yang et al, 2004) in blood samples collected at follow-up. Genomic DNA was isolated from peripheral blood leukocytes using Puregene Blood Core Kit C with Clotspin Baskets to extract blood clots, and then sodium bisulfite treated using the EZ-96 DNA Methylation Kit, converting non-methylated cytosine residues into uracil (Zymo Research, Orange, CA).…”

Section: Methodsmentioning

confidence: 99%

“…LINE-1 elements make up approximately 17% of the human genome (Lander et al, 2001), and the methylation extent of these regions may provide an indication of whether compounds are epigenetically active (Nelson et al, 2011). Hypomethylation of LINE-1 elements has been associated with genomic instability (Belancio et al, 2009), risk of cancer (Belancio et al, 2010), ischemic heart disease, stroke, and hypertension (Baccarelli et al, 2010), increased LDL-C, and decreased high density lipoprotein cholesterol (HDL-C) (Cash et al, 2011), as well as age, sex, race, ethnicity, and environmental exposures (Nelson et al, 2011). …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Associations between serum perfluoroalkyl acids and LINE-1 DNA methylation

Watkins

Wellenius

Butler

et al. 2014

Environment International

Self Cite

View full text Add to dashboard Cite

Perfluoroalkyl acids (PFAAs) are persistent, synthetic compounds that are used in a number of consumer products. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been associated with cardiovascular risk factors, and changes in gene expression and DNA methylation in animals and cellular systems. However, whether PFAA exposure is associated with LINE-1 DNA methylation, a potential marker of cardiovascular risk, in humans remains unknown. We sought to evaluate the cross-sectional associations between serum PFAAs and LINE-1 DNA methylation in a population highly exposed to PFOA. We measured serum PFAAs twice four to five years apart in 685 adult participants (47% male, mean age ± SD=42 ± 11 years). We measured percent LINE-1 DNA methylation in peripheral blood leukocytes at the second time point (follow-up), and estimated absolute differences in LINE-1 methylation associated with an interquartile (IQR) shift in mean PFAA serum levels. IQR increases in mean serum PFOA, PFOS, perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were associated with differences of −0.04 (p=0.16), 0.20 (p=0.001), 0.06 (p=0.19), and 0.02 (p=0.57), respectively, in % LINE-1 methylation at follow-up after adjustment for potential confounders. We observed a monotonic increase in LINE-1 DNA methylation across tertiles of PFOS and PFNA (ptrend=0.02 for both associations), but not across tertiles of PFOA or PFHxS (ptrend=0.71 and 0.44, respectively). In summary, serum PFOS was associated with LINE-1 methylation, while serum PFOA, PFHxS, and PFNA were not. Additional research is needed to more precisely determine whether these compounds are epigenetically active.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Associations between serum perfluoroalkyl acids and LINE-1 DNA methylation

Watkins

Wellenius

Butler

et al. 2014

Environment International

Self Cite

View full text Add to dashboard Cite

show abstract

“…27 Cash et al, reported that global DNA hypomethylation (measured in LINE-1 elements) was associated with altered levels of LDL and HDL, both risk factors of CVD, in peripheral blood samples from Samoan islanders. 28 Most of these studies were cross-sectional and they were not able to determine the causal direction of this relationship.…”

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

View full text Add to dashboard Cite

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.

show abstract

“…This mark has been recently related to BMI [22][23][24] type 2 diabetes and insulin resistance [25,26], cardiovascular disease [27], and inflammatory responses [28]. SERPINE-1 gene encodes the plasminogen activator inhibitor (PAI-1), which is a fibrinolysis inhibitor, and SERPINE-1 methylation levels have been previously associated with obesity and metabolic syndrome [29].…”

Section: Introductionmentioning

confidence: 99%