UMOD Polymorphisms Associated With Kidney Function, Serum Uromodulin and Risk of Mortality Among Patients With Chronic Kidney Disease, Results From the C-STRIDE study

Abstract Background: Several genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in uromodulin (UMOD) gene, such as 12917707, rs4293393, rs6497476 and rs13333226, as susceptibility genetic variants associated with chronic kidney disease (CKD) based on the case-control study design. We aimed to explore the associations of the variants with baseline phenotypes and prospective prognosis of CKD among 2731 Chinese patients with CKD stage 1-4. Polymorphisms of rs11864909, rs4293393, rs6497476 and rs13333226 were genotyped using the Sequenom MassARRAY iPLEX platform.Results: rs13333226 and rs4293393 were in complete linkage disequilibrium. Based on the T dominant model, T allele of rs11864909 was associated with baseline levels of eGFR and serum uromodulin with linear regression coefficients of 2.68 (95% confidence interval [CI]: 0.61, 4.96) and -12.95(95%CI: -17.59, -7.98), respectively, after adjustment for cardiovascular and kidney specific risk factors. After a median follow-up of 4.94 years, both G allele of rs4293393/rs13333226 and C allele of rs6497476 were associated with reduced risk of all-cause mortality with multivariable adjusted hazard ratios of 0.341(95%CI: 0.105, 0.679) and 0.344(95%CI: 0.104, 0.671), respectively. However, no associations were found between the variants and eGFR slope in the linear mix effect model.Conclusions: Variant of rs11864909 in the UMOD gene was associated with levels of eGFR and serum uromodulin, while those of rs4293393 and rs6497476 associated with all-cause mortality among patients with CKD.