Genetic variations in the sodium balance-regulating genes ENaC, NEDD4L, NDFIP2 and USP2 influence blood pressure and hypertension

Hyun Seok Jin, Kyung Won Hong, Ji Eun Lim, Sue Yun Hwang, Sang Ho Lee, Chol Shin, Hun Kuk Park, Bermseok Oh

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background/Aims: In humans, the kidneys regulate blood pressure by balancing sodium concentrations. Fine-tuning of renal sodium reabsorption and excretion depends on the epithelial sodium channel protein (ENaC: protein complex of SCNN1A, SCNN1B, and SCNN1G). The surface expression of ENaC components is directed by the ubiquitination of ENaC by NEDD4L, an ENaC-specific E3 ubiquitin ligase, and is regulated by the deubiquitination of ENaC by USP2. The activity of NEDD4L in turn is regulated by phosphorylation by SGK1 and also through interaction with NDFIP2. Methods: We analyzed 91 SNPs in 7 genes using the genotype data of 8,842 individuals from the Korea Association REsource subject pool for their correlation with blood pressure and hypertension. Results: 25 SNPs in the SCNN1A, SCNN1B, SCNN1G, NEDD4L, NDFIP2, and USP2 loci were found to be associated with blood pressure. An additional hypertension case-control study identified 13 SNPs in SCNN1B, SCNN1G, and NEDD4L that were linked to hypertension. Conclusion: These results support our hypothesis that individual variations in blood pressure are attributed to variants of the genes that regulate renal sodium reabsorption and excretion. Our data also suggest that it would be meaningful to investigate the role of NEDD4L-mediated ubiquitination in the pathogenesis of hypertension.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalKidney and Blood Pressure Research
Volume33
Issue number1
DOIs
Publication statusPublished - 2010 Mar 1

Fingerprint

Sodium
Blood Pressure
Hypertension
Single Nucleotide Polymorphism
Ubiquitination
Genes
Epithelial Sodium Channels
Ubiquitin-Protein Ligases
Korea
Case-Control Studies
Proteins
Genotype
Phosphorylation
Kidney
Renal Reabsorption
Renal Elimination

Keywords

  • Blood pressure
  • ENaC
  • Hypertension
  • NDFIP2
  • NEDD4L
  • USP2

ASJC Scopus subject areas

  • Nephrology
  • Cardiology and Cardiovascular Medicine

Cite this

Genetic variations in the sodium balance-regulating genes ENaC, NEDD4L, NDFIP2 and USP2 influence blood pressure and hypertension. / Jin, Hyun Seok; Hong, Kyung Won; Lim, Ji Eun; Hwang, Sue Yun; Lee, Sang Ho; Shin, Chol; Park, Hun Kuk; Oh, Bermseok.

In: Kidney and Blood Pressure Research, Vol. 33, No. 1, 01.03.2010, p. 15-23.

Research output: Contribution to journalArticle

Jin, Hyun Seok ; Hong, Kyung Won ; Lim, Ji Eun ; Hwang, Sue Yun ; Lee, Sang Ho ; Shin, Chol ; Park, Hun Kuk ; Oh, Bermseok. / Genetic variations in the sodium balance-regulating genes ENaC, NEDD4L, NDFIP2 and USP2 influence blood pressure and hypertension. In: Kidney and Blood Pressure Research. 2010 ; Vol. 33, No. 1. pp. 15-23.
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