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

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.

Identification of New Genes and Genetic Variant Loci Associated with Breast Muscle Development in the Mini-Cobb F2 Chicken Population Using a Genome-Wide Association Study

“…NEDD4-like E3 ubiquitin protein ligase ( NEDD4L ) encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. In humans, NEDD4L is involved in the process of several diseases, including the inhibition of hepatocellular carcinoma cell growth [ 62 ] and involvement in viral replication [ 63 ], while its mutation is associated with hypertension in chronic kidney disease [ 64 ]. Currently, there are no functional studies on this gene in chickens.…”

NEDD4L is a promoter for angiogenesis and cell proliferation in human umbilical vein endothelial cells

“…Many previous studies established the association of NEDD4L with cardiovascular disease. A series of clinical and basic research have demonstrated that NEDD4L is associated with hypertension 17–20 . Our recent work has proved that NEDD4L participated in miR‐30a‐attenuated atherosclerosis 21 .…”

“…A series of clinical and basic research have demonstrated that NEDD4L is associated with hypertension. 17 , 18 , 19 , 20 Our recent work has proved that NEDD4L participated in miR‐30a‐attenuated atherosclerosis. 21 Nonetheless, the role of NEDD4L on endothelial cells has yet to be fully illustrated.…”