A single nucleotide polymorphism in the UMOD promoter is associated with end stage renal disease

Chen, Tingyu; Wang, Qianliao; Li, Guisen; Wang, Li

doi:10.1186/s12881-016-0358-3

Cited by 5 publications

(3 citation statements)

References 31 publications

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“…Several common UMOD variants (rs12917707, rs4293393, rs11864909, rs13329952) are associated with both CKD and eGFR (Köttgen et al, 2009, 2010; Gudbjartsson et al, 2010; Pattaro et al, 2012, 2016). More recently, the higher frequency in ESRD of another common UMOD variant (rs13333226), has been confirmed in 638 Chinese patients with ESRD and 366 controls (Chen et al, 2016). Several common variants in the myosin heavy chain type II isoform A ( MYH9 ) gene have been associated with non-diabetic ESRD in African Americans (Kao et al, 2008; Kopp et al, 2008; Chambers et al, 2010).…”

Section: Introductionmentioning

confidence: 93%

Genetic Susceptibility to Chronic Kidney Disease – Some More Pieces for the Heritability Puzzle

et al. 2019

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Chronic kidney disease (CKD) is a major global health problem with an increasing prevalence partly driven by aging population structure. Both genomic and environmental factors contribute to this complex heterogeneous disease. CKD heritability is estimated to be high (30–75%). Genome-wide association studies (GWAS) and GWAS meta-analyses have identified several genetic loci associated with CKD, including variants in UMOD, SHROOM3 , solute carriers, and E3 ubiquitin ligases. However, these genetic markers do not account for all the susceptibility to CKD, and the causal pathways remain incompletely understood; other factors must be contributing to the missing heritability. Less investigated biological factors such as telomere length; mitochondrial proteins, encoded by nuclear genes or specific mitochondrial DNA (mtDNA) encoded genes; structural variants, such as copy number variants (CNVs), insertions, deletions, inversions and translocations are poorly covered and may explain some of the missing heritability. The sex chromosomes, often excluded from GWAS studies, may also help explain gender imbalances in CKD. In this review, we outline recent findings on molecular biomarkers for CKD (telomeres, CNVs, mtDNA variants, sex chromosomes) that typically have received less attention than gene polymorphisms. Shorter telomere length has been associated with renal dysfunction and CKD progression, however, most publications report small numbers of subjects with conflicting findings. CNVs have been linked to congenital anomalies of the kidney and urinary tract, posterior urethral valves, nephronophthisis and immunoglobulin A nephropathy. Information on mtDNA biomarkers for CKD comes primarily from case reports, therefore the data are scarce and diverse. The most consistent finding is the A3243G mutation in the MT-TL1 gene, mainly associated with focal segmental glomerulosclerosis. Only one GWAS has found associations between X-chromosome and renal function (rs12845465 and rs5987107). No loci in the Y-chromosome have reached genome-wide significance. In conclusion, despite the efforts to find the genetic basis of CKD, it remains challenging to explain all of the heritability with currently available methods and datasets. Although additional biomarkers have been investigated in less common suspects such as telomeres, CNVs, mtDNA and sex chromosomes, hidden heritability in CKD remains elusive, and more comprehensive approaches, particularly through the integration of multiple –“omics” data, are needed.

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Section: Introductionmentioning

confidence: 93%

Genetic Susceptibility to Chronic Kidney Disease – Some More Pieces for the Heritability Puzzle

et al. 2019

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“…Gómez et al 19 found a missense mutation p.V458L in which leucine variant was more frequent in individuals with reduced GFR as compared to healthy individuals with normal GFR. Associations of UMOD rs13333226 G allele with hypertension, CKD 20 and ESRD 26 have been reported. However, Cui et al 27 reported association of rs13333226G allele with slower decline in renal function in individuals with CKD.…”

Section: Discussionmentioning

confidence: 99%

Uromodulin rs4293393 T>C variation is associated with kidney disease in patients with type 2 diabetes

et al. 2017

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Background & objectives:Uromodulin, a UMOD gene encoded glycoprotein is synthesized exclusively in renal tubular cells and released into urine. Mutations lead to uromodulin misfolding and retention in the kidney, where it might stimulate cells of immune system to cause inflammation and progression of kidney disease. Genome-wide association studies (GWAS) have identified UMOD locus to be associated with hypertension and diabetic nephropathy (DN). In this study, we investigated the association between rs4293393 variation in UMOD gene and susceptibility to kidney disease in individuals with type 2 diabetes mellitus (T2DM).Methods:A total of 646 individuals, 208 with T2DM without evidence of kidney disease (DM), 221 with DN and 217 healthy controls (HC) were genotyped for UMOD variant rs4293393T>C by restriction fragment length polymorphism. Serum uromodulin levels were quantified by enzyme-linked immunosorbent assay.Results:A significant difference was found in genotype and allelic frequency among DM, DN and HC. TC+CC genotype and C allele were found more frequently in DN compared to HC (33.9 vs 23.0%, P=0.011 and 20.1 vs 12.9%, P=0.004, respectively). Compared to DM, C allele was found to be more frequent in individuals with DN (20.1 vs 14.7%, P=0.034). Those with DN had higher serum uromodulin levels compared to those with DM (P=0.001). Serum uromodulin levels showed a positive correlation with serum creatinine (r=0.431; P<0.001) and negative correlation with estimated glomerular filtration rate (r=−0.423; P<0.001).Interpretation & conclusions:The frequency of UMOD rs4293393 variant with C allele was significantly higher in individuals with DN. UMOD rs4293393 T>C variation might have a bearing on susceptibility to nephropathy in north Indian individuals with type 2 diabetes.

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“…The etiologies of many diseases have been attributed to SNPs, and their identification has contributed to the pathophysiology of different types of CKD [3,5]. For example, the presence of susceptibility variants in particular gene loci (e.g., the loci of UMOD and APOL1), may increase the risk of CKD and increase the possibility of end stage renal disease (ESRD) in specific populations [6,7]. Namely, APOL1 polymorphisms, which are found as homozygous recessive risk alleles in approximately 10% of the African American population, are now recognized as risk factors that increase the progression of hypertensive and glomerular kidney diseases [7].…”

Section: Introductionmentioning

confidence: 99%

Implementation of a Renal Precision Medicine Program: Clinician Attitudes and Acceptance

Spiech

Tripathy

Woodcock

et al. 2020

Life

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A precision health initiative was implemented across a multi-hospital health system, wherein a panel of genetic variants was tested and utilized in the clinical care of chronic kidney disease (CKD) patients. Pharmacogenomic predictors of antihypertensive response and genomic predictors of CKD were provided to clinicians caring for nephrology patients. To assess clinician knowledge, attitudes, and willingness to act on genetic testing results, a Likert-scale survey was sent to and self-administered by these nephrology providers (N = 76). Most respondents agreed that utilizing pharmacogenomic-guided antihypertensive prescribing is valuable (4.0 ± 0.7 on a scale of 1 to 5, where 5 indicates strong agreement). However, the respondents also expressed reluctance to use genetic testing for CKD risk stratification due to a perceived lack of supporting evidence (3.2 ± 0.9). Exploratory sub-group analyses associated this reluctance with negative responses to both knowledge and attitude discipline questions, thus suggesting reduced exposure to and comfort with genetic information. Given the evolving nature of genomic implementation in clinical care, further education is warranted to help overcome these perception barriers.

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A single nucleotide polymorphism in the UMOD promoter is associated with end stage renal disease

Cited by 5 publications

References 31 publications

Genetic Susceptibility to Chronic Kidney Disease – Some More Pieces for the Heritability Puzzle

Genetic Susceptibility to Chronic Kidney Disease – Some More Pieces for the Heritability Puzzle

Uromodulin rs4293393 T>C variation is associated with kidney disease in patients with type 2 diabetes

Implementation of a Renal Precision Medicine Program: Clinician Attitudes and Acceptance

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