UMOD as a susceptibility gene for end-stage renal disease
1 Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, A. Deusinglaan 1, Groningen, 9713AV, the Netherlands
2 Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany
3 Department of Epidemiology, Unit of Genetic Epidemiology & Bioinformatics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
4 Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
5 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
6 Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
BMC Medical Genetics 2012, 13:78 doi:10.1186/1471-2350-13-78Published: 5 September 2012
In recent genetic association studies, common variants including rs12917707 in the UMOD locus have shown strong evidence of association with eGFR, prevalent and incident chronic kidney disease and uromodulin urinary concentration in general population cohorts. The association of rs12917707 with end-stage renal disease (ESRD) in a recent case-control study was only nominally significant.
To investigate whether rs12917707 associates with ESRD, graft failure (GF) and urinary uromodulin levels in an independent cohort, we genotyped 1142 ESRD patients receiving a renal transplantation and 1184 kidney donors as controls. After transplantation, 1066 renal transplant recipients were followed up for GF. Urinary uromodulin concentration was measured at median [IQR] 4.2 [2.2-6.1] yrs after kidney transplantation.
The rs12917707 minor allele showed association with lower risk of ESRD (OR 0.89 [0.76-1.03], p = 0.04) consistent in effect size and direction with the previous report (Böger et al, PLoS Genet 2011). Meta-analysis of these findings showed significant association of rs12917707 with ESRD (OR 0.91 [0.85-98], p = 0.008). In contrast, rs12917707 was not associated with incidence of GF. Urinary uromodulin concentration was lower in recipients-carriers of the donor rs12917707 minor allele as compared to non-carriers, again consistent with previous observations in general population cohorts.
Our study thus corroborates earlier evidence and independently confirms the association between UMOD and ESRD.