Common variation in the WNK1 gene and blood pressure in childhood: the Avon Longitudinal Study of Parents and Children.
WNK1 gene variants have been associated with adult blood pressure. We aimed to investigate relationships between WNK1 variants and blood pressure, as well as blood pressure change with age, in a longitudinal childhood study. Associations between single nucleotide polymorphisms in WNK1 and blood pressure and the rate of blood pressure change between 7 and 11 years were examined in the Avon Longitudinal Study of Parent and Children Study (n=5326 for systolic blood pressure at 11 years). We observed associations (P<0.05) with diastolic blood pressure gradient with age for 33 of 82 typed and imputed polymorphisms, including polymorphisms in exons 4, 10, and 11 (rs10774466, rs1012729, and rs9804992). The minor allele (G) of rs1012729 (frequency: 25.6%) was associated with a gender-adjusted change in a diastolic blood pressure gradient of -0.11 mm Hg/y (95% CI: -0.20 to -0.03 mm Hg/y; P=0.0054). No associations were shown with the systolic blood pressure gradient. At age 11 years, 30 polymorphisms showed association (P<0.05) with systolic blood pressure, including variants in exons 4 and 10 (rs10774466 and rs1012729). Only 3 polymorphisms were associated with diastolic blood pressure at 11 years. In exploration of polymorphism-dietary cation interactions on systolic blood pressure at 11 years, 59 reached significance (P<0.05; 12.3 expected by chance), mostly (n=33) related to dietary calcium. The findings show that common intronic and exonic WNK1 variants are associated with diastolic blood pressure gradient from 7 to 11 years and with systolic blood pressure at 11 years. Our study suggests that previously reported effects of WNK1 variants on blood pressure are mediated via effects on the gradient of blood pressure change with age.
Tobin
Martin D
MD
Departments of Health Sciences and Genetics, Genetic Epidemiology Group, University of Leicester, Leicester, United Kingdom. mt47@le.ac.uk
Timpson
Nicholas J
NJ
Wain
Louise V
LV
Ring
Susan
S
Jones
Louise R
LR
Emmett
Pauline M
PM
Palmer
Thomas M
TM
Ness
Andrew R
AR
Samani
Nilesh J
NJ
Smith
George Davey
GD
Burton
Paul R
PR
D000375:Aging / Q000235:genetics*; D000483:Alleles; D001794:Blood Pressure / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004739:England; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008137:Longitudinal Studies; D008297:Male; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000076204:WNK Lysine-Deficient Protein Kinase 1
D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human