Single-nucleotide polymorphism of the UMOD promoter is associated with the outcome of chronic kidney disease patients.

Uromodulin (UMOD) is the most abundant protein secreted in urine and the mutated form of the UMOD gene is associated with UMOD-associated kidney disease (UAKD). Although UMOD accumulates in the kidney of UAKD patients, it is unclear whether this also occurred in the chronic kidney disease (CKD) patients. Therefore, the association of single-nucleotide polymorphisms (SNPs) in the promoter region of UMOD gene with the kidney survival time of CKD was investigated. The promoter region of the UMOD gene was sequenced for 111 CKD patients. The Kaplan-Meier method was used to identify the disease outcome associated with SNPs in the promoter region of the UMOD gene in CKD patients. The Cox proportional hazard model was used to identify risk factors for the kidney survival time of CKD. SNPs in reference to GenBank accession NG-000016 were detected at 23 sites of the 481-bp in the UMOD promoter region from the CKD patients and the healthy controls. The 6 SNPs with minor allele frequency >5% in the CKD patients or controls were used for disease risk and outcome analysis. The frequent allele rs13333226AA was associated with a shorter period of kidney survival time in CKD patients (P=0.005). The length of kidney survival time in CKD patients with the rs13333226AA genotype was significantly shorter than that of patients with the frequent allele rs13333226AG+GG (relative risk, 0.361; 95% confidence interval, 0.171-0.761; P=0.007). In conclusion, analysis of genetic polymorphisms in UMOD may help to identify the CKD patient subgroups at a high risk for a disease outcome, thereby helping to refine therapeutic decisions in CKD patients.