Common variants of the UMOD promoter associated with blood pressure in a community-based Chinese cohort

Han, Juan; Chen, Yuqing; Liu, Ying; Yu, Liang; Wang, Xingyu; Liu, Lisheng; Wang, Fang; Zhang, Luxia; Zhang, Hong; Wang, Haiyan

doi:10.1038/hr.2012.51

Cited by 19 publications

(18 citation statements)

References 25 publications

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“…Common variants in the promoter of the UMOD gene are linked to hypertension, CKD, and kidney stones (13)(14)(15)(16)(17). They also affect uromodulin excretion (19).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the rare mutations causing ADTKD, genome-wide association studies have evidenced robust associations between common variants near the UMOD gene and urinary uromodulin levels, hypertension, eGFR, and renal function decline over time (1,(13)(14)(15)(16)(17). These common variants, which form a linkage disequilibrium block in the promoter of UMOD, are associated with increased renal expression and urinary levels of uromodulin (18,19).…”

Section: Introductionmentioning

confidence: 99%

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Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion

Troyanov

Delmas-Frenette

Bollée

et al. 2016

Clinical Journal of the American Society of Nephrology

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Background and objectives The urinary excretion of uromodulin is influenced by common variants in the UMOD gene, and it may be related to NaCl retention and hypertension. Levels of uromodulin are also dependent of the renal function, but other determinants remain unknown.Design, setting, participants, & measurements We tested associations between the urinary excretion of uromodulin; medical history and medication; serum and urinary levels of electrolytes, glucose, and uric acid; and the genotype at the UMOD/Protein Disulfide Isomerase-Like, Testis Expressed locus (rs4293393 and rs12446492); 943 participants from the CARTaGENE Cohort, a random sample from the Canadian population of 20,004 individuals, were analyzed. Participants with available genotyping were obtained from a substudy addressing associations between common variants and cardiovascular disease in paired participants with high and low Framingham risk scores and vascular rigidity indexes.Results The population studied was 5469 years old, with 51% women and eGFR of 9614 ml/min per 1.73 m 2 . Uromodulin excretion was 25 (11-42) mg/g creatinine. Using linear regression, it was independently higher among patients with higher eGFR, the TT genotype of rs4293393, and the TT genotype of rs12446492. The fractional excretions of urate and sodium showed a strong positive correlation with uromodulin, likely linked to the extracellular volume status. The presence of glycosuria and the use of uricosuric drugs, which both increased the fraction excretion of urate, were independently associated with a lower uromodulin excretion, suggesting novel interactions between uric acid and uromodulin excretion. ConclusionsIn this large cohort, the excretion of uromodulin correlates with clinical, genetic, and urinary factors. The strongest associations were between uric acid, sodium, and uromodulin excretions and are likely linked to the extracellular volume status.

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“…Common variants in the promoter of the UMOD gene are linked to hypertension, CKD, and kidney stones (13)(14)(15)(16)(17). They also affect uromodulin excretion (19).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion

Troyanov

Delmas-Frenette

Bollée

et al. 2016

Clinical Journal of the American Society of Nephrology

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“…A previous case-control association study showed that G allele of rs13333226 was independently associated with a decreased risk of nephropathy, and the G allele was also associated with a higher eGFR and lower systolic blood pressure in the study cohort [27]. However, two other studies have shown that G allele carriers have higher diastolic blood pressure and higher plasma uric acid compared with A/A homozygotes [18, 19]. …”

Section: Discussionmentioning

confidence: 88%

“…Lots of studies revealed that the variants of UMOD were associated with different risk of CKD, cardiovascular disease, hypertension, and hyperuricemia, T allele of rs12917707 was associated with lower risk of CKD and ESRD [9, 10, 18, 19, 23, 24]. But the relationship between variants of UMOD and risk of kidney disease was complicated, the several rare mutation in UMOD gene has been described as a cause of uromodulin-associated kidney disease, an autosomal dominant disease [25, 26].…”

Section: Discussionmentioning

confidence: 99%

“…And the minor allele frequency of rs12917707 (T allele) was only 1% in Han Chinese (http://hapmap.ncbi.nlm.nih.gov/index.html.en). Another single nucleotide polymorphism (SNP) in the promoter region of UMOD gene, rs13333226, was reported to be associated with hypertension, and serum uric level [18, 19]. The G allele carriers had higher diastolic blood pressure and higher plasma uric acid compared with A/A homozygotes [18, 19].…”

Section: Introductionmentioning

confidence: 99%

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

Chen¹,

Wang²,

et al. 2016

BMC Med Genet

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BackgroundSeveral genome-wide association studies revealed that several variants of UMOD gene were related to the estimated glomerular filtration rate (eGFR), CKD or hypertension. In this study, we investigated the association between a common variant rs13333226 in the promoter region of UMOD gene and end stage renal disease (ESRD).MethodsVariant rs13333226 of UMOD gene was genotyped by using the ABI Real time TaqMan allelic discrimination assay in a case-control study including 638 unrelated patients with ESRD and 366 controls.ResultsThe frequency of UMOD SNP rs13333226 GG/GA genotype was significantly higher (36.83% vs. 20.22%, P = 4.02 × 10-8) and the frequency of G allele was much higher (19.04% vs. 11.20%, P = 4.00 × 10−6) in the patients with ESRD than in the controls. The G allele was associated with an increased risk of ESRD (odds ratio 2.30, 95% confidence interval 1.70–3.11, P = 6.10 × 10−8). And G allele (odds ratio 2.33, 95% confidence interval 1.32–4.13, P = 3.65 × 10−3) was associated independently with ESRD.ConclusionsA common variation rs13333226 in the promoter region of UMOD gene was independently associated with ESRD in Han Chinese.

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Na⁺‐K⁺‐2Cl⁻Cotransporter (NKCC) Physiological Function in Nonpolarized Cells and Transporting Epithelia

Delpire¹,

Gagnon²

2018

Comprehensive Physiology

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Two genes encode the Na -K -2Cl cotransporters, NKCC1 and NKCC2, that mediate the tightly coupled movement of 1Na , 1K , and 2Cl across the plasma membrane of cells. Na -K -2Cl cotransport is driven by the chemical gradient of the three ionic species across the membrane, two of them maintained by the action of the Na /K pump. In many cells, NKCC1 accumulates Cl above its electrochemical potential equilibrium, thereby facilitating Cl channel-mediated membrane depolarization. In smooth muscle cells, this depolarization facilitates the opening of voltage-sensitive Ca channels, leading to Ca influx, and cell contraction. In immature neurons, the depolarization due to a GABA-mediated Cl conductance produces an excitatory rather than inhibitory response. In many cell types that have lost water, NKCC is activated to help the cells recover their volume. This is specially the case if the cells have also lost Cl . In combination with the Na /K pump, the NKCC's move ions across various specialized epithelia. NKCC1 is involved in Cl -driven fluid secretion in many exocrine glands, such as sweat, lacrimal, salivary, stomach, pancreas, and intestine. NKCC1 is also involved in K -driven fluid secretion in inner ear, and possibly in Na -driven fluid secretion in choroid plexus. In the thick ascending limb of Henle, NKCC2 activity in combination with the Na /K pump participates in reabsorbing 30% of the glomerular-filtered Na . Overall, many critical physiological functions are maintained by the activity of the two Na -K -2Cl cotransporters. In this overview article, we focus on the functional roles of the cotransporters in nonpolarized cells and in epithelia. © 2018 American Physiological Society. Compr Physiol 8:871-901, 2018.

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Common variants of the UMOD promoter associated with blood pressure in a community-based Chinese cohort

Cited by 19 publications

References 25 publications

Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion

Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion

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

Na⁺‐K⁺‐2Cl⁻Cotransporter (NKCC) Physiological Function in Nonpolarized Cells and Transporting Epithelia

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Common variants of the UMOD promoter associated with blood pressure in a community-based Chinese cohort

Cited by 19 publications

References 25 publications

Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion

Clinical, Genetic, and Urinary Factors Associated with Uromodulin Excretion

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

Na+‐K+‐2Cl−Cotransporter (NKCC) Physiological Function in Nonpolarized Cells and Transporting Epithelia

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Na⁺‐K⁺‐2Cl⁻Cotransporter (NKCC) Physiological Function in Nonpolarized Cells and Transporting Epithelia