Polymorphisms in the WNK1 gene are associated with blood pressure variation and urinary potassium excretion
| Autor: | Eric J. Brunner, Abiodun Onipinla, Michael Marmot, G. Mark Lathrop, Susana Eyheramendy, Paul Elliott, Meena Kumari, Robert Clarke, Richard Dobson, Maris Laan, Nilesh J. Samani, Mark J. Caulfield, Philip Howard, Francesco P. Cappuccio, Chen Ji, Jaspal S. Kooner, John M. C. Connell, Kate L. Lee, Martin Farrall, Elin Org, Stephen Newhouse, Margus Viigimaa, Mimoza Hoti, Rory Collins, Morris J. Brown, Anna F. Dominiczak, Beverley Burke, Pasquale Strazzullo, Peeter Juhanson, Roberto Iacone, Catriona Wallace, Patricia B. Munroe, John C. Chambers, Gudrun Veldre, Sue Shaw-Hawkins |
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| Přispěvatelé: | Wallace, Chris [0000-0001-9755-1703], Apollo - University of Cambridge Repository, Newhouse, S, Farrall, M, Wallace, C, Hoti, M, Burke, B, Howard, P, Onipinla, A, Lee, K, Shaw Hawkins, S, Dobson, R, Brown, M, Samani, Nj, Dominiczak, Af, Connell, Jm, Lathrop, Gm, Kooner, J, Chambers, J, Elliott, P, Clarke, R, Collins, R, Laan, M, Org, E, Juhanson, P, Veldre, G, Viigimaa, M, Eyheramendy, S, Cappuccio, Fp, Ji, C, Iacone, Roberto, Strazzullo, Pasquale, Kumari, M, Marmot, M, Brunner, E, Caulfield, M, Munroe, Pb |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Candidate gene lcsh:Medicine Blood Pressure 030204 cardiovascular system & hematology Essential hypertension Cohort Studies 0302 clinical medicine WNK Lysine-Deficient Protein Kinase 1 WNK1 gene lcsh:Science Genetics and Genomics/Genetics of Disease Genetics 0303 health sciences Multidisciplinary Intracellular Signaling Peptides and Proteins Middle Aged Protein-Serine-Threonine Kinases 3. Good health Science & Technology - Other Topics Female Research Article Adult medicine.medical_specialty General Science & Technology Single-nucleotide polymorphism Genetics and Genomics/Complex Traits Biology Protein Serine-Threonine Kinases Polymorphism Single Nucleotide Cardiovascular Disorders/Hypertension Minor Histocompatibility Antigens 03 medical and health sciences Internal medicine Genetics and Genomics/Population Genetics MD Multidisciplinary medicine Humans Polymorphism Allele 030304 developmental biology Science & Technology MULTIDISCIPLINARY SCIENCES Haplotype lcsh:R Case-control study Odds ratio medicine.disease QP Endocrinology Blood pressure Case-Control Studies Potassium lcsh:Q |
| Zdroj: | PLoS ONE, Vol 4, Iss 4, p e5003 (2009) PLOS ONE, 4 (4), Article e5003. (2009) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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 = 7×10−3, combined with BRIGHT data-set p = 2×10−4, 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−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 |
| Databáze: | OpenAIRE |
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