Common variation in with no-lysine kinase 1 (WNK1) and blood pressure responses to dietary sodium or potassium interventions- family-based association study.
BACKGROUND
Common variations in the gene with no-lysine kinase 1 (WNK1) are associated with hypertension, but because of gene-environment interaction, it is difficult to fully identify the genetic contribution of WNK1 gene polymorphism to blood pressure (BP) variability. The aim of this study was to identify the effect of common WNK1 variants on the shift of BP during strict dietary interventions of salt or potassium intake.


RESULTS
A total of 342 subjects from 126 families were selected and sequentially maintained on normal diet for 3 days at baseline, a low-salt diet for 7 days (3g/day, NaCl), then a high-salt diet for 7 days (18 g/day), and high-salt diet with potassium supplementation for another 7 days (4.5 g/day, KCl). Five single nucleotide polymorphisms (SNPs) were selected from the WNK1 gene. rs880054 and rs12828016 were associated with diastolic BP (DBP) response during the low-or high-sodium intervention, and rs2301880 was significantly associated with systolic BP, DBP and mean arterial pressure responses to the high-sodium intervention (all P<0.05). Unfortunately, no associations for WNK1 SNPs and the constructed haplotype blocks of WNK1 with BP responses to high-salt-and-potassium supplement intervention reached nominal statistical significance.


CONCLUSIONS
The WNK1 gene might be mechanistically involved in the variation in BP response to dietary sodium and potassium intake among individuals, and might contribute to the variation of this complex phenotype.
Department of Cardiovascular, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, China.
Fuqiang
F
Liu
Shuhui
S
Zheng
Jianjun
J
Mu
Chao
C
Chu
Lan
L
Wang
Yang
Y
Wang
Hongyu
H
Xiao
Dan
D
Wang
Yu
Y
Cao
Keyu
K
Ren
Enqi
E
Liu
Zuyi
Z
Yuan
D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D005190:Family; D005260:Female; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide; D011189:Potassium Chloride / Q000008:administration & dosage*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D000076204:WNK Lysine-Deficient Protein Kinase 1
D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D017673:Sodium Chloride, Dietary; D011189:Potassium Chloride; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human