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Lack of family-based association between common variations in WNK1 and blood pressure level.

ABSTRACT: WNK1 (With No-lysine Kinase 1) modulates numerous sodium transport-related ion channels involved in regulation of blood pressure. Several studies have indicated associations between the common variants of the WNK1 gene and hypertension or blood pressure levels. However, little data exists on Asian populations and normotensive or pre-hypertensive subjects. Our aim was to detect whether the common variations in the WNK1 gene are potential contributors to individual variations in blood pressure in a family-based sample.525 individuals from 116 families were selected from a rural community of Northern China. Five single-nucleotide polymorphisms were selected from the WNK1 gene. Single-marker and haplotype analyses were conducted using the Family-Based Association Test program.Regretful, no associations for the 5 WNK1 SNPs and the constructed haplotype blocks of WNK1 with blood pressure level reached nominal statistical significance.We conclude that although multiple candidate genes are involved in development of hypertension, the genetic polymorphism in WNK1 is not a major contributor to the observed variability in blood pressure and familial clustering risk of hypertension.

SUBMITTER: Liu F

PROVIDER: S-EPMC4211417 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Lack of family-based association between common variations in WNK1 and blood pressure level.

Liu Fuqiang F Lian Qiufang Q Ren Jie J Ren Keyu K Wang Yang Y Wang Dan D Chu Chao C Wang Lan L Guo Tongshuai T Liu Enqi E Mu Jianjun J Yuan Zuyi Z

Medical science monitor : international medical journal of experimental and clinical research 20141016

<h4>Background</h4>WNK1 (With No-lysine Kinase 1) modulates numerous sodium transport-related ion channels involved in regulation of blood pressure. Several studies have indicated associations between the common variants of the WNK1 gene and hypertension or blood pressure levels. However, little data exists on Asian populations and normotensive or pre-hypertensive subjects. Our aim was to detect whether the common variations in the WNK1 gene are potential contributors to individual variations in ...[more]

PMID: 25321950

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Project description:WNK1--a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control--is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23-4.9), DBP 1.9 mmHg (95%CI:0.7-3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0-1.7]).We genotyped this variant in six independent populations (n = 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7 x 10(-3), combined with BRIGHT data-set p = 2 x 10(-4), n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p<10(-7)). We identified several common haplotypes to be associated with increased BP and multiple low frequency haplotypes significantly associated with lower BP (>10 mmHg reduction) and risk for hypertension (OR<0.60). Our data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH.

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Lack of family-based association between common variations in WNK1 and blood pressure level.

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Lack of family-based association between common variations in WNK1 and blood pressure level.

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