Abstract
BackgroundIn 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.MethodsTo 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.ResultsThe 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.ConclusionsOur study thus corroborates earlier evidence and independently confirms the association between UMOD and ESRD.
Highlights
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
Identification of the genetic variants involved in its susceptibility and progression to end-stage renal disease (ESRD) will improve our understanding of biological mechanisms
Among them a prominent place is taken by UMOD which has been reproducibly identified in multiple cohorts as one of the top loci associated with renal function parameters [7,8,9,10]
Summary
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. Chronic kidney disease (CKD) is a significant and increasing global challenge for public health It affects 10% of the general population in industrialized nations, incurring high morbidity and mortality, and posing a substantial financial burden to the health care systems [1,2,3]. It is a complex, multifactorial disorder with an important genetic component. All the studies showed a consistent trend of association of the rs12917707 minor allele with lower risk of CKD [7,11,12,13,14,15], and the minor alleles of SNPs in perfect LD with rs12917707, rs4293393 and rs13333226, were associated with lower urinary uromodulin levels [11,15]
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