A Variant in the NEDD4L Gene Associates With Hypertension in Chronic Kidney Disease in the Southeastern Han Chinese Population

Am J Hypertens. 2020 Apr 1;33(4):341-349. doi: 10.1093/ajh/hpaa015.

Abstract

Background: "Neuronal precursor cell expressed developmentally down-regulated 4-like" (NEDD4L) is considered a candidate gene for hypertension-both functionally and genetically-through the regulation of the ubiquitination of the epithelial sodium channel (ENaC). This study explores the relationship between genetic variation in NEDD4L and hypertension with chronic kidney disease (CKD) in the southeastern Han Chinese population.

Methods: We recruited 623 CKD patients and measured ambulatory blood pressure monitoring (ABPM), and the rs4149601 and rs2288774 polymorphisms in NEDD4L were genotyped using quantitative polymerase chain reaction.

Results: For rs4149601, significant differences in genotype frequencies in an additive model (GG vs. GA vs. AA) were observed between normotensive patients and hypertensive patients when hypertension was classified into ambulatory hypertension, clinical hypertension, and ambulatory systolic hypertension (P = 0.038, 0.005, and 0.006, respectively). In a recessive model (GG + GA vs. AA), the frequency of the AA genotype of rs4149601 in the hypertension groups was all higher than that in the normotensive groups. The genotype distribution of rs2288774 did not differ significantly between the normotensive and hypertensive patients. In both the full cohort and the propensity score matching (PSM) cohort, the AA genotype of rs4149601 (compared with the GG + GA genotype group) was independently correlated with ambulatory hypertension, clinical hypertension, and ambulatory systolic hypertension by multivariate logistic regression analysis.

Conclusions: The present study indicates that the AA genotype of rs4149601 associates with hypertension in CKD. Consequently, the rs4149601 A allele might be a risk factor for hypertension with CKD.

Keywords: NEDD4L; ambulatory; blood pressure; blood pressure monitoring; chronic kidney disease; epithelial sodium channel; hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People / genetics
  • Blood Pressure / genetics*
  • China / epidemiology
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Hypertension / diagnosis
  • Hypertension / ethnology
  • Hypertension / genetics*
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Nedd4 Ubiquitin Protein Ligases / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Propensity Score
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / ethnology
  • Renal Insufficiency, Chronic / genetics*
  • Renal Insufficiency, Chronic / physiopathology
  • Risk Assessment
  • Risk Factors
  • Young Adult

Substances

  • Nedd4 Ubiquitin Protein Ligases
  • Nedd4L protein, human