DNA Hypermethylation and Inflammatory Markers in Incident Japanese Dialysis Patients

Abstract

Background/Aims: Inflammation is an established mortality risk factor in chronic kidney disease (CKD) patients. Although a previous report showed that uremic Caucasian patients with inflammation had signs of global DNA hypermethylation, it is still unknown whether DNA hypermethylation is linked to inflammatory markers including a marker of bacterial infections in Japanese CKD patients. Methods: In 44 consecutive incident dialysis patients (26 males, mean age 59 ± 12 years) without clinical signs of infection, global DNA methylation was evaluated in peripheral blood DNA using the Hpa II /Msp I ratio by the luminometric methylation assay method. A lower ratio of Hpa II /Msp I indicates global DNA hypermethylation. Procalcitonin (PCT), a marker of inflammation due to bacterial infections, was measured using an immunochromatographic assay. Results: The patients were divided into hyper- and hypomethylation groups based on the median value of the Hpa II /Msp I ratio 0.31 (range 0.29–0.37). Whereas patients in the hypermethylation group had higher ferritin levels [133.0 (51.5–247.3) vs. 59.5 (40.0–119.0) ng/ml; p = 0.046], there were no significant differences in age, gender, diabetes, smoking, anemia or serum albumin levels. However, the Hpa II /Msp I ratio showed significant negative correlations with PCT (ρ = –0.32, p = 0.035) and ferritin (ρ = –0.33, p = 0.027) in Spearman’s rank test. In a multiple linear regression analysis, PCT and ferritin were associated with a lower Hpa II /Msp I ratio (R 2 = 0.24, p = 0.013). Conclusion: In this study, global DNA hypermethylation was associated with ferritin and, most likely, PCT, suggesting that inflammation induced by subclinical bacterial infection promoted DNA methylation.