Predictors of methylation in Leukocyte DNA

Altered DNA methylation is associated with various diseases. An international research team led by Nuria Malats, from CNIO, Madrid, where Manolis Kogevinas from the CREAL, ISGlobal alliance center, has participated, 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 nearby 900 control participants from the Spanish Bladder Cancer/EPICURO study. This paper was published in Environmental Health Perspective.

DNA methylation plays a fundamental role in regulation of gene expression, genomic imprinting, X-chromosome inactivation, and repression of transposable elements. Aberrant DNA methylation has been associated with various cancers and with developmental, autoimmune, and other chronic diseases. Global DNA methylation can be estimated based on methylation of repetitive sequences such as Alu elements or long interspersed nuclear element 1 (LINE-1). Age, sex, smoking, and arsenic and lead exposures have been associated with DNA methylation.

The international researcher team has determined LINE-1 methylation levels by pyrosequencing. Individual data included demographics, smoking status, nutrient intake, concentrations of 12 trace elements in nail, xenobiotic metabolism gene variants, and more than 500 polymorphisms among 24 genes in the one-carbon metabolism pathway. “We have assessed the association between LINE-1 methylation levels (percentage of methylated cytosines) and potential determinants”, said Kogevinas.

The results of the study indicate that women had lower levels of LINE-1 methylation than men, and people who smoked blond tobacco showed lower methylation than nonsmokers. Arsenic toenail concentration was inversely associated with LINE-1 methylation. By contrast, iron and nickel were positively associated with LINE-1 methylation. Single nucleotide polymorphisms (SNPs) were associated with LINE-1 methylation. 

“Assessing the impact of both genetic and non-genetic factors on global DNA methylation may improve our understanding of the molecular pathogenesis of many common diseases. Therefore, we investigated associations of global DNA methylation in LINE-1 with different variants. We have identified several characteristics, environmental factors, and common genetic variants that predicted DNA methylation among study participants”, concludes Kogevinas.

Reference

Tajuddin SM, Amaral AF, Fernandez AF, Rodriguez-Rodero S, Rodriguez RM, Moore LE, Tardón A, Carrato A, García-Closas M, Silverman DT, Jackson BP, García-Closas R, Cook AL, Cantor KP, Chanock SJ, Kogevinas M, Rothman N, Real FX, Fraga MF, Malats N.Genetic and Non-genetic Predictors of LINE-1 Methylation in Leukocyte DNA. Environ Health Perspect 2013; 121(6): 650-656.

Image: Leukocyte (Wikipedia)