UMOD as a susceptibility gene for end-stage renal disease
UMOD as a susceptibility gene for end-stage renal disease
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DOI：
10.1186/1471-2350-13-78
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发表时间：
2012-09-05
影响因子：
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通讯作者：
Navis, Gerjan
中科院分区：
文献类型：
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作者：
Reznichenko, Anna;Boeger, Carsten A.;Navis, Gerjan
背景：在最近的遗传关联研究中，UMOD 基因座中包括 rs12917707 在内的常见变异已显示出与普通人群中 eGFR、流行和偶发的慢性肾病以及尿调节素尿浓度相关的有力证据。在最近的一项病例对照研究中，rs12917707 与终末期肾病 (ESRD) 的关联仅具有名义上的显着性。 方法：为了在独立队列中研究 rs12917707 是否与 ESRD、移植失败 (GF) 和尿调节素水平相关，我们对 1142 名接受肾移植的 ESRD 患者和 1184 名肾捐献者作为对照进行了基因分型。移植后，对 1066 名肾移植受者进行了 GF 随访。肾移植后中位数 [IQR] 4.2 [2.2-6.1] 年测量尿尿调节素浓度。 结果：rs12917707 小等位基因显示与 ESRD 风险较低相关（OR 0.89 [0.76-1.03]，p = 0.04），其效应大小和方向与之前的报告一致（Boger 等人，PLoS Genet 2011）。这些结果的荟萃分析显示 rs12917707 与 ESRD 显着相关（OR 0.91 [0.85-98]，p = 0.008）。相反，rs12917707 与 GF 的发生率无关。与非携带者相比，供体 rs12917707 次要等位基因的接受者携带者的尿液尿调节素浓度较低，这再次与之前在一般人群队列中的观察结果一致。 结论：因此，我们的研究证实了早期的证据，并独立证实了 UMOD 与 ESRD 之间的关联。
Background: 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.Methods: 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.Results: 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 (Boger 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.Conclusions: Our study thus corroborates earlier evidence and independently confirms the association between UMOD and ESRD.