Genetic and Non-genetic Predictors of LINE-1 Methylation in Leukocyte DNA

Abstract

Background: Altered DNA methylation has been associated with various diseases.Objective: We evaluated the association between levels of methylation in leukocyte DNA at long interspersed nuclear element 1 (LINE-1) and genetic and non-genetic characteristics of 892 control participants from the Spanish Bladder Cancer/EPICURO study.Methods: We determined LINE-1 methylation levels by pyrosequencing. Individual data included demographics, smoking status, nutrient intake, toenail concentrations of 12 trace elements, xenobiotic metabolism gene variants, and 515 polymorphisms among 24 genes in the one-carbon metabolism pathway. To assess the association between LINE-1 methylation levels (percentage of methylated cytosines) and potential determinants, we estimated beta coefficients (βs) by robust linear regression.Results: Women had lower levels of LINE-1 methylation than men (β = –0.7, p = 0.02). Persons who smoked blond tobacco showed lower methylation than nonsmokers (β = –0.7, p = 0.03). Arsenic toenail concentration was inversely associated with LINE-1 methylation (β = –3.6, p = 0.003). By contrast, iron (β = 0.002, p = 0.009) and nickel (β = 0.02, p = 0.004) were positively associated with LINE-1 methylation. Single nucleotide polymorphisms (SNPs) in DNMT3A (rs7581217-per allele, β = 0.3, p = 0.002), TCN2 (rs9606756-GG, β = 1.9, p = 0.008; rs4820887-AA, β = 4.0, p = 4.8 × 10–7; rs9621049-TT, β = 4.2, p = 4.7 × 10–9), AS3MT (rs7085104-GG, β = 0.7, p = 0.001), SLC19A1 (rs914238, TC vs. TT: β = 0.5 and CC vs. TT: β = –0.3, global p = 0.0007) and MTHFS (rs1380642, CT vs. CC: β = 0.3 and TT vs. CC; β = –0.8, global p = 0.05) were associated with LINE-1 methylation.Conclusions: We identified several characteristics, environmental factors, and common genetic variants that predicted DNA methylation among study participants.

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

“…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.…”

“…13 It is well known that several of these environmental exposures are associated with risk of complex diseases, such as Type 2 diabetes mellitus (T2DM).…”

Environmental factors in cardiovascular disease

“…Studies have been conducted in the USA, China, and Spain to evaluate the association between exposure to lead and DNA methylation, generally discovering a trend towards hypomethylation. [235][236][237][238] In an epigenome-wide association study, 235 exposure to lead was negatively associated with methylation of a CpG site in the promoter of the COL1A2 gene. Exposure to lead in particulate matter is also related to the expression of microRNAs that are involved in oxidative stress and inflammation.…”

LINE-1 DNA methylation: A potential forensic marker for discriminating monozygotic twins

“…Tajuddin et al [32] evaluated the association between LINE-1 methylation levels and genetic and non-genetic characteristics of 892 control participants form the Spanish Bladder Cancer/EPICURO study, and found that women had lower levels of LINE-1 methylation than men. van Bemme et al [19] also reported that buffy coat LINE-1 methylation levels differed by sex, with males having higher methylation than females in their study.…”