Relationship Between Polymorphism Of The UMOD Gene Promoter Region And The Outcome Of Kidney In Chronic Kidney Disease

Objective Chronic kidney disease(CKD) constitutes a serious public health burden worldwide. CKD can progress to ESRD that requires dialysis or transplant- tation. In addition to major known risk factors for CKD-hypertension, heperlipemia diabetes, smoking and so on, multiple studies have provided evidence for a genetic component to kidney disease. Uromodulin is exclusivel- y synthesized in the kidney, encoded by UMOD gene and play an important role in the occurrence and progress of CKD. A genome-wide association studies(GWAS) in 2009, identified single nucleotide polymorphisms in the region of the UMOD gene have been shown to be associated with chronic kidney disease and reduced glomerular filtration rate. But it is rare researched about the association between single nucleotide polymorphisms in the region of the UMOD gene and the the outcome of kidney in chronic kidney disease patients. Our research wants to investigate the relationship between single nucleotide polymorphisms(SNPs) in the UMOD gene promoter region and the outcome of kidney in chronic kidney disease patients. Researching new markers that can estimate the outcome of kidney.Methods:This is a case-control study. Blood samples were obtained from 95 CKD patients from the inpatient of the Fourth Hospital of Hebei Medical University between 2002 and 2008. Blood samples were also collected from 104 healthy controls. The presence of CKD was defined in accordance with the 2002 National Kidney Foundation Kidney Disease Outcomes Quality Initiative(K-DOQI). The promoter region of UMOD gene was sequenced by using polymerasechain reaction method. The relationship between the polymorphis- ms in UMOD gene promoter and the outcome of kidney was analysed. The χ2 test was used to analyze dichotomous values, such as the presence or absence of an individual SNP in CKD patients and healthy controls. The kidney survival curve was calculated using the Kaplan-Meier method, and compared with the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazards model. All statistical analyses were performed using the SPSS17.0 software(SPSS Company, Chicago, IL, USA). For all the statistical tests, P<0.05 was considered statistically significant.Results:1 SNPs were detected at 23 sites of the 481-bp in the UMOD promoter region from the CKD patients and the healthy controls. The frequency of the three sites-1, 945\-1,660\-1, 617(rs13333226)are greater than 5 percent. And the frequency of rs13333226 is higher in the CKD patients. But, correcting the risk factor of CKD, there is no association between the SNP of rs13333226 and CKD.2 Single factor analysis showed that smoking people had shorter survival time of kidney than unsmoking people(χ2=3.883, P=0.049); People with higher mean artery pressure(MAP) had shorter survival time of kidney than people with lower MAP(χ2=6.260, P=0.012); People with massive proteinuria had shorter survival time of kidney than people with small amounts of protein in the urine(χ2=7.698, P=0.006). The survival time of kidney in patients with G allele was significantly longer than patients with A allele at rs13333226 site(χ2=6.078, P=0.014). The main risk factor were screend by Cox regression analysis showing that G allele is the independent protective factor for the outcome of kidney in patient with CKD.Conclusion:1 In the northern Chinese population, there are three single nucleotide polymorphisms sites of UMOD gene, they are-1,945\-1,660\-1,617(rs13333226).2 There is no association between single nucleotide polymorphisms in the region of the UMOD gene and CKD.3 SNPs in UMOD gene promoter are independent prognostic factors for patients with CKD and it is conducive to the early prediction of the prognosis of CKD patients. Positive effective therapy should be performed on patients with estimated shorter survival to improve their survival rate.