Correlations in global DNA methylation measures in peripheral blood mononuclear cells and granulocytes

Abstract

Alterations in global DNA methylation levels have been associated with chronic diseases. Despite the increase in the number of studies measuring markers of global methylation, few have adequately examined within-individual differences by source of DNA and whether within-individual differences by source of DNA differ by age, race and other lifestyle factors. We examined correlations between peripheral mononuclear cell (PBMC) and granulocyte DNA methylation levels measured by the luminometric methylation assay (LUMA), and in LINE-1, Sat2, and Alu by MethyLight and pyrosequencing, in the same individual in 112 women participating in The New York City Multiethnic Breast Cancer Project. Levels of DNA methylation of Sat2 by MethyLight (r = 0.57; P < 0.01) and LINE-1 by pyrosequencing (r = 0.30; P < 0.01) were correlated between PBMC and granulocyte DNA of the same individuals, but LUMA and Alu levels were not. The magnitude of the correlations for Sat2 and LINE-1 varied when stratified by selected demographic and lifestyle factors, although the study sample size limited our comparisons across subgroups. These results lend further support to the importance of considering the source of DNA in epidemiologic studies of white blood cell DNA methylation. Results from studies that combine individuals with different available DNA sources need to be interpreted with caution.

Keywords: Alu; DNA methylation; LINE-1; LUMA; LUMA, Luminometric methylation assay; PBMC, peripheral mononuclear cell; Sat2.

Figure 1.

Correlation plots of peripheral blood mononuclear cells (PBMC) and granulocyte DNA methylation percentages for LINE-1 and Sat2 in the New York City Multiethnic Breast Cancer Project.

Figure 2.

Correlation plots of LINE-1 methylation by pyrosequencing and MethyLight measures in peripheral mononuclear cells (PBMC) (A), and granulocytes (B) in the New York City Multiethnic Breast Cancer Project.