International comparison of genomic variations for prognostic factors in chronic kidney disease

炎症是慢性肾脏病(CKD)患者公认的死亡危险因素，感染可能是导致炎症的原因之一。我们在瑞典的合作肾病小组显示，发炎的尿毒症高加索患者有全球DNA高甲基化的迹象。我们调查了日本CKD患者的DNA超甲基化与炎症标志物有关，包括细菌感染的标志。全球DNA超甲基化与铁蛋白和降钙素原作为细菌感染的标志有关，这表明由亚临床细菌感染引起的炎症促进了DNA甲基化。此外，全球DNA超甲基化与近期的炎症状态有关，提示超甲基化状态与现在和未来的炎症状态之间可能存在一个轴。这些结果强烈表明，控制尿毒症引起的感染和免疫功能障碍可能是诱发CKD患者炎症的重要因素。

Inflammation is an established mortality risk factor in chronic kidney disease (CKD) patients and infection may contribution to induce inflammation. Our collaborating Nephrology group in Sweden showed that inflamed uremic Caucasian patients had signs of global DNA hyper-methylation. We have investigated that DNA hyper-methylation is linked to inflammatory markers including a marker of bacterial infections in Japanese CKD patients.Global DNA hyper-methylation was associated with ferritin and procalcitonin as a marker of bacterial infection, suggesting that inflammation induced by subclinical bacterial infection promoted DNA methylation. Moreover, Global DNA hyper-methylation was associated with near future inflammatory status, suggesting a possible axis between hyper-methylation status and present as well as future inflammatory status.These results strongly suggest that to control infection and immune dysfunction due to uremia may be important to induce inflammation in CKD patients.