The Relationship Between Global DNA Methylation And Plasma Asymmetric Dimethylarginine In Patients With Chronic Kidney Disease

BackgroundChronic kidney disease(CKD) is a long term condition caused by damage to both kidneys.There is no single cause and the damage is usually irreversible and can lead to ill health.It is helpful that understanding the pathogenesis of CKD can prevent and treatment patients with this disease effectively.Resent increasing evidence indicates the aberrant of expression of many genes were key factors in the progression of CKD.DNA methylation has emergerd as an important epigenetic modification that regulates the expression and function of the genes without altering the primary sequence of the DNA in the mammalian genome.Thus we are hypothesized that DNA methylation may mediate the development of CKD by influence the expression of some genes related with CKD.To investigate the levels of global DNA methylation in patients with CKD could let us learn more about the pathogenesis and progression of CKD. Asymmetric dimethylarginine(ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor that has been found to be an independent predictor of cardiovascular morbidity and mortality.In patients with chronic kidney disease especially with end-stage renal disease(ESRD),many studies have shown that the concentration of plasma ADMA is obviously higher than healthy people and it also has an association with cardiovascular disease(CVD) in these patients. However,the mechanism by which factors regulation of ADMA expression is unclear.Recently,dimethylarginine dimethylaminohydrolase(DDAH) a key enzyme for removal of ADMA has been discovered inactivation through the hypermethylation of the promoter region of DDAH gene.However,the association between global DNA methylation and plasma ADMA is not reported.ObjectiveThe purposes of these studies are:1.To analyze the changes of global DNA methylation in patients with CKD 5th stage that non-dialysis.2.Detection of plasma ADMA in patients above.3.To study the relationship between global DNA methylation and plasma ADMA.Methods40 of CKD 5th stage non-dialysis in patients were diagnosed according to the US K/DOQI in our department(The GFR was measured by applying the modified MDRD equation).32 healthy participants from our medical examination center as a control.The procedures for the experiment as followings1.Collecting both clinical characteristics and biochemical indicators.2.Extracting leukocyte genomic DNA.3.Detecting levels of global leukocyte genomic DNA methylation and plasma ADMA by using high performance liquid chromatography.4.Date analysis is using SPSS 13.0 statistic software.Results1.The level of global DNA methylation,CKD group is higher than that of control group(4.498%±0.109%vs 4.428%±0.096%,P＜0.01).The change was also seen in the concentration of plasma ADMA(0.563μmol/L±0.193μmol/L vs 0.454μmol/L±0.137μmol/L,P＜0.01)2.There are a negative relationship between with global DNA methylation and the serum albumin(r=-0.438,P=0.002) in the CKD group,while,a positive relation of DNA methylation and BUN(r=0.353,P=0.012) also was observed.3.In CKD group,the concentration of plasma ADMA is associated with both global DNA methylation(r=0.324,P=0.034) and serum creatinine (r=0.315,P=0.038).Conclusion1.Both the global DNA methylation and levels of plasma ADMA in patients with CKD 5th stage that non-dialysis were higher than that of control.2.DNA hypermethylation may elevate the concentration of plasma ADMA in patients with CKD.3.Aberrant DNA methylation in patients with CKD may play a very important role in the CKD complication of cardiovascular disease.