Kidney Week

Abstract: SA-PO777

Association Between Polymorphism of rs11864909 and Serum Uromodulin Among CKD Was Modified by Kidney Function

Session Information

• CKD: Epidemiology, Risk Factors, Prevention - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1901 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Wang, Jinwei, Renal Division, Department of Medicine, Peking University First Hospital; Peking University Institute of Nephrology, Beijing, BEIJING, China

Jinwei Wang,

• Zhang, Luxia, Peking University Institute of Nephrology, Beijing, China

Luxia Zhang,

• He, Kevin, Kidney Epidemiology and Cost Center, University of Michgian, Ann Arbor, Michigan, United States

Kevin He,

• Zhao, Minghui, Reanl division, Peking University First Hospital,, Beijing, China

Minghui Zhao,

Group or Team Name

• the Chinese Cohort Study of Chronic Kidney Disease

Background

The single nucleotide polymorphism (SNP) of rs11864909 is located close to uromodulin gene of UMOD. A genome-wide association study in east Asian populations detected a genome-wide significant association between the SNP and estimated glomerular filtration rate (eGFR). We aimed to test the association of the SNP with serum uromodulin among patients with chronic kidney disease (CKD) and test if the association was modified by eGFR.

Methods

Altogether, 1812 participants with complete relevant clinical and genotyping data in the Chinese Cohort Study of CKD (n=3499) was enrolled in the study. Genotyping for rs11864909 was conducted by TaqMan genotyping assay. Serum uromodulin was measured by a commercially available ELISA kit. Linear regression analysis was used to test the association between rs11864909 and serum uromodulin.

Results

The mean age of the population was 48.4±13.7 years, with 56.9% of males. The mean level of eGFR was 52.5±30.5ml/min/1.73m². The proportions of patients with CKD stage 1, 2, 3 and 4 were 15.3%, 16.8%, 41.2% and 26.7%, respectively. The mean level of serum uromodulin was 90.9±61.2 ng/mL. The CC, CT and TT genotype of the rs11864909 polymorphism accounted for 72.7%, 24.7% and 2.6% of the population (P for Hardy-Weinberg equilibrium>0.05). People with the CT&TT genotype had a significantly lower level of serum uromodulin than those with CC genotype (79.7 ng/mL vs. 95.1 ng/mL, P<0.001). After inclusion of the interaction term between rs11864909 and eGFR (P for interaction<0.001) in the multi-variable adjusted linear regression model, the regression coefficient (standard error) per 1 ml/min/1.73m² increase in eGFR increased from 1.4(0.039) to 1.5(0.045), while the effect of rs11864909 (CT&TT vs. CC) lost statistical significance (regression coefficient increased from -20.6[2.3] to -2.1[4.6]). Sensitivity analysis among those with CKD stages 3 and 4 and those from large central study sites got consistent results.

Conclusion

The common polymorphism of rs11864909 in the UMOD gene associated with the level of serum uromodulin among patients with CKD, but the relationship was influenced by kidney function. The results add further insights into the effect of UMOD gene among CKD.

Funding

• Government Support - Non-U.S.