DNA hypermethylation and inflammatory markers in incident Japanese dialysis patients.

DNA hypermethylation and inflammatory markers in incident Japanese dialysis patients.
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DOI:
10.1159/000339437
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发表时间:
2012-01
期刊:
影响因子:
--
通讯作者:
Maruyama S
Maruyama S
中科院分区:
其他
文献类型:
--
作者:
Kato S;Lindholm B;Stenvinkel P;Ekström TJ;Luttropp K;Yuzawa Y;Yasuda Y;Tsuruta Y;Maruyama S

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炎症是慢性肾脏病(CKD)患者的既定死亡风险因素。尽管先前的报告显示,尿毒症白人炎症患者有整体DNA超甲基化的迹象,但仍不清楚DNA超甲基化是否与日本CKD患者的炎症标志物(包括细菌感染标志物)有关。在44例无感染临床体征的连续事件透析患者(26例男性,平均年龄59 ± 12岁)中,通过发光甲基化测定法使用HpaII/MspI比值评价外周血DNA的总体DNA甲基化。HpaII/MspI比值较低表明整体DNA超甲基化。降钙素原(PCT)是细菌感染引起的炎症标志物,使用免疫层析测定法进行测量。根据HpaII/MspI比值的中位数0.31(范围0.29-0.37),将患者分为高甲基化组和低甲基化组。而高甲基化组患者的铁蛋白水平较高[133.0(51.5-247.3)vs. 59.5(40.0-119.0)ng/ml; p = 0.046],年龄、性别、糖尿病、吸烟、贫血或血清白蛋白水平无显著差异。然而,在斯皮尔曼秩检验中,HpaII/MspI比值与PCT(ρ =-0.32,p = 0.035)和铁蛋白(ρ =-0.33,p = 0.027)呈显著负相关。在多元线性回归分析中,PCT和铁蛋白与较低的HpaII/MspI比值相关(R2 = 0.24,p = 0.013)。在这项研究中,整体DNA超甲基化与铁蛋白相关,最有可能与PCT相关,这表明亚临床细菌感染诱导的炎症促进了DNA甲基化。
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. 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. 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 (R2 = 0.24, p = 0.013). 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.
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