DNA hypermethylation and inflammatory markers in incident Japanese dialysis patients.
OBJECTIVE
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 HpaII/MspI ratio by the luminometric methylation assay method. A lower ratio of HpaII/MspI 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 HpaII/MspI 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 HpaII/MspI 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 HpaII/MspI ratio (R(2) = 0.24, p = 0.013).


CONCLUSIONS
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.
Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Sawako
S
Kato
Bengt
B
Lindholm
Peter
P
Stenvinkel
Tomas J
TJ
Ekström
Karin
K
Luttropp
Yukio
Y
Yuzawa
Yoshinari
Y
Yasuda
Yoshinari
Y
Tsuruta
Shoichi
S
Maruyama