Genetic polymorphisms of the urea transporter gene are associated
with antihypertensive response to nifedipine GITS

Hong, Xiumei; Huang, Xing; Yu, Yafen; Zhang, Y.; Zhang, S.; Tang, Genfu; Xu, Xiping

doi:10.1358/mf.2007.29.1.1063490

Cited by 15 publications

(9 citation statements)

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“…The importance of microvascular function is emphasised by the solute carrier transporters such as SLC14A2 encoding a urea transporter, which has previously been linked to autosomal dominant Streeten type orthostatic hypotensive disorder 41 and BP response to nifedipine, a calcium channel blocker antihypertensive drug 42 . SLC8A1 encodes a sodium calcium exchanger expressed in cardiomyocytes which alters cardiac contractility and hypertrophy and shows abnormal BP in SLC8A1 transgenic mice 43 .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Warren¹,

Εvangelou²,

Cabrera³

et al. 2017

Nat Genet

506

452

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Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. Combined with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure raising genetic variants on future cardiovascular disease risk.

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Section: Discussionmentioning

confidence: 99%

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Warren¹,

Εvangelou²,

Cabrera³

et al. 2017

Nat Genet

506

452

View full text Add to dashboard Cite

show abstract

“…Several polymorphisms of UT-A2 have been identified in humans. Although the functional consequence of these variants on urea transport have not been explored to our knowledge, epidemiological studies in large populations revealed that some of these variants are associated with blood pressure and metabolic syndrome, [217][218][219] suggesting that UT-A2 and renal urea handling influence fluid balance in humans. New studies should address the function of these variants and attempt to better define the contribution of UT-A2 to overall urea handling.…”

Section: Discussionmentioning

confidence: 99%

New insights into urea and glucose handling by the kidney, and the urine concentrating mechanism

Bankir

Yang

2012

Kidney International

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The mechanism by which urine is concentrated in the mammalian kidney remains incompletely understood. Urea is the dominant urinary osmole in most mammals and may be concentrated a 100-fold above its plasma level in humans and even more in rodents. Several facilitated urea transporters have been cloned. The phenotypes of mice with deletion of the transporters expressed in the kidney have challenged two previously well-accepted paradigms regarding urea and sodium handling in the renal medulla but have provided no alternative explanation for the accumulation of solutes that occurs in the inner medulla. In this review, we present evidence supporting the existence of an active urea secretion in the pars recta of the proximal tubule and explain how it changes our views regarding intrarenal urea handling and UT-A2 function. The transporter responsible for this secretion could be SGLT1, a sodium-glucose cotransporter that also transports urea. Glucagon may have a role in the regulation of this secretion. Further, we describe a possible transfer of osmotic energy from the outer to the inner medulla via an intrarenal Cori cycle converting glucose to lactate and back. Finally, we propose that an active urea transporter, expressed in the urothelium, may continuously reclaim urea that diffuses out of the ureter and bladder. These hypotheses are all based on published findings. They may not all be confirmed later on, but we hope they will stimulate further research in new directions.

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“…Other 3 SNPs (rs1825475, rs1484873, and rs7232775) in SLC14A2 on chromosome 18 were known to be associated with serum creatinine and GFR [ 15 ]. rs1484873 and rs7232775 in SLC14A2 on chromosome 18 were also associated with BUN and hypertension [ 16 , 17 ]. rs10937329 in an intergenic region was the lead SNP on chromosome 3 associated with BUN.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association analysis identifies multiple loci associated with kidney disease-related traits in Korean populations

Lee

Park

et al. 2018

PLoS ONE

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Chronic kidney disease (CKD) is an important social health problem characterized by a decrease in the kidney glomerular filtration rate (GFR). In this study, we analyzed genome-wide association studies for kidney disease-related traits using data from a Korean adult health screening cohort comprising 7,064 participants. Kidney disease-related traits analyzed include blood urea nitrogen (BUN), serum creatinine, estimated GFR, and uric acid levels. We detected two genetic loci (SLC14A2 and an intergenic region) and 8 single nucleotide polymorphisms (SNPs) associated with BUN, 3 genetic loci (BCAS3, C17orf82, ALDH2) and 6 SNPs associated with serum creatinine, 3 genetic loci (BCAS3, C17orf82/TBX2, LRP2) and 7 SNPs associated with GFR, and 14 genetic loci (3 in ABCG2/PKD2, 2 in SLC2A9, 3 in intergenic regions on chromosome 4; OTUB1, NRXN2/SLC22A12, CDC42BPG, RPS6KA4, SLC22A9, and MAP4K2 on chromosome 11) and 84 SNPs associated with uric acid levels. By comparing significant genetic loci associated with serum creatinine levels and GFR, rs9895661 in BCAS3 and rs757608 in C17orf82 were simultaneously associated with both traits. The SNPs rs11710227 in intergenic regions on chromosome 3 showing significant association with BUN is newly discovered. Genetic variations of multiple gene loci are associated with kidney disease-related traits, and differences in associations between kidney disease-related traits and genetic variation are dependent on the population. The meanings of the mutations identified in this study will need to be reaffirmed in other population groups in the future.

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Genetic polymorphisms of the urea transporter gene are associated with antihypertensive response to nifedipine GITS

Cited by 15 publications

References 0 publications

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

New insights into urea and glucose handling by the kidney, and the urine concentrating mechanism

Genome-wide association analysis identifies multiple loci associated with kidney disease-related traits in Korean populations

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