HYPertension in ESTonia (HYPEST), the British Genetics of Hypertension (BRIGHT); additional BRIGHT consortium members are given in Supp. Text S1.
Research Article
You have full text access to this OnlineOpen article
Novel polymorphic AluYb8 insertion in the WNK1 gene is associated with blood pressure variation in Europeans†
Article first published online: 10 MAY 2011
DOI: 10.1002/humu.21508
© 2011 Wiley-Liss, Inc.
Additional Information
How to Cite
Putku, M., Kepp, K., Org, E., Sõber, S., Comas, D., Viigimaa, M., Veldre, G., Juhanson, P., Hallast, P., Tõnisson, N., HYPEST, Shaw-Hawkins, S., Caulfield, M. J., BRIGHT, Khusnutdinova, E., Kožich, V., Munroe, P. B. and Laan, M. (2011), Novel polymorphic AluYb8 insertion in the WNK1 gene is associated with blood pressure variation in Europeans. Hum. Mutat., 32: 806–814. doi: 10.1002/humu.21508
- †
Communicated by Pui-Yan Kwok
Publication History
- Issue published online: 27 JUN 2011
- Article first published online: 10 MAY 2011
- Accepted manuscript online: 21 APR 2011 01:28PM EST
- Manuscript Accepted: 28 MAR 2011
- Manuscript Received: 6 DEC 2010
Funded by
- Wellcome Trust International Senior Research Fellowships. Grant Numbers: 070191/Z/03/Z (to M.L.), 070255/Z/03/Z (to V.K.) in Biomedical Science in Central Europe
- The BRIGHT study was supported by the Medical Research Council of Great Britain. Grant Number: G9521010D
- British Heart Foundation. Grant Number: PG02/128
- The Barts and The London Charity
- The HYPEST study was supported by the Estonian Ministry of Education and Science. Grant Number: 0182721s06
- HHMI International Scholarship. Grant Number: 55005617 (to M.L.)
- Estonian Science Foundation. Grant Number: ETF7471 (to M.L.; stipend for M.P.)
- The CADCZ study was supported by the Ministry of Health of the Czech Republic. Grant Number: NS10036-4/2008 (to V.K.)
References
- , . 2002. Alu repeats and human genomic diversity. Nat Rev Genet 3:370–379.
- , , , , . 2007. Genetic structure of chimpanzee populations. PLoS Genet 3:e66.
- , , . 2008. Mammalian non-LTR retrotransposons: for better or worse, in sickness and in health. Genome Res 18:343–358.
- , , , , , , . 2008. Active Alu retrotransposons in the human genome. Genome Res 18:1875–1883.
- . 2003. Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem 72:291–336.
- , . 2006. Retrotransposable elements and human disease. Genome Dis 1:104–115.
- , , , , , , , , , , , , , , , , , , , , , . 2003. Genome-wide mapping of human loci for essential hypertension. Lancet 361:2118–2123.
- , , , , , , , , . 2000. Alu insertion polymorphisms in NW Africa and the Iberian Peninsula: evidence for a strong genetic boundary through the Gibraltar Straits. Hum Genet 107:312–319.
- , . 2009. The impact of retrotransposons on human genome evolution. Nat Rev Genet 10:691–703.
- , , , , , , . 2003. Multiple promoters in the WNK1 gene: one controls expression of a kidney-specific kinase-defective isoform. Mol Cell Biol 23:9208–9221.
- , . 2008. Tuning in to the signals: noncoding sequence conservation in vertebrate genomes. Trends Genet 24:344–352.
- , , , , , . 2004. Distinguishing humans from great apes with AluYb8 repeats. J Mol Biol 339:721–729.
- , , , . 2005. Segmental duplications and gene conversion: human luteinizing hormone/chorionic gonadotropin beta gene cluster. Genome Res 15:1535–1546.
- . 2000. Conserved noncoding sequences are reliable guides to regulatory elements. Trends Genet 16:369–372.
- , . 2006. Alu elements as regulators of gene expression. Nucleic Acids Res 34:5491–5497.
- , , , , , , , . 2000. Deletion allele of angiotensin-converting enzyme gene increases risk of essential hypertension in Japanese men: the Suita Study. Circulation 101:2060–2065.
- , , , , , , , , , , , , . 2003. Genetic variants of homocysteine metabolizing enzymes and the risk of coronary artery disease. Mol Genet Metab 79:167–175.
- , , , , , , , , , . 2008. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat Genet 40:592–599.
- , , , , , , , , . 2004. Identification of 108 SNPs in TSC, WNK1, and WNK4 and their association with hypertension in a Japanese general population. J Hum Genet 49:507–515.
- , , . 2001. Molecular mechanisms of human hypertension. Cell 104:545–556.
- , , , . 2002. Processing of gene expression data generated by quantitative real-time RT-PCR. Biotechniques 32:1372–1374, 1376, 1378–1379.
- , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , . 2009. Polymorphisms in the WNK1 gene are associated with blood pressure variation and urinary potassium excretion. PLoS One 4:e5003.
- , , , , , , , , , , , , , , . 2005. Haplotypes of the WNK1 gene associate with blood pressure variation in a severely hypertensive population from the British Genetics of Hypertension study. Hum Mol Genet 14:1805–1814.
- , , , , , , , . 1998. Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation 97:1766–1772.
- , , , , , , , . 2009. Variations in the WNK1 gene modulates the effect of dietary intake of sodium and potassium on blood pressure determination. J Hum Genet 54:474–478.
- , , , , , , , , , , , . 2010. The effects of sex and method of blood pressure measurement on genetic associations with blood pressure in the PAMELA study. J Hypertens 28:465–477.
- , . 2004. Cis-acting regulatory variation in the human genome. Science 306:647–650.
- , , , , , . 2004. Absence of the TAP2 human recombination hotspot in chimpanzees. PLoS Biol 2:e155.
- , , . 2000. EMBOSS: the European Molecular Biology Open Software Suite. Trends Genet 16:276–277.
- , , , , , . 1990. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86:1343–1346.
- , . 2000. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132:365–386.
- , , , , , . 2007. Gender differences in kidney function. Pflugers Arch 455:397–429.
- , , . 2002. Angiotensin I-converting enzyme gene polymorphism in a Serbian population: a gender-specific association with hypertension. Scand J Clin Lab Invest 62:469–475.
- , , , , , , , , , , , , , , , . 2005. Association of WNK1 gene polymorphisms and haplotypes with ambulatory blood pressure in the general population. Circulation 112:3423–3429.
- , , , , , , , , , , . 2008. Common variation in the WNK1 gene and blood pressure in childhood: the Avon Longitudinal Study of Parents and Children. Hypertension 52:974–979.
- , , , . 2005. WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic. Hypertension 46:758–765.
- . 2007. Heritable forms of hypertension. Pediatr Nephrol 24:1929–1937.
- , . 2001. WNK kinases, a novel protein kinase subfamily in multi-cellular organisms. Oncogene 20:5562–5569.
- , , . 2009. Genomic views of distant-acting enhancers. Nature 461:199–205.
- , , , , , , , , . 2001. Patterns of ancestral human diversity: an analysis of Alu-insertion and restriction-site polymorphisms. Am J Hum Genet 68:738–752.
- , , , , , , , , , , , , , . 2003. Genetic variation among world populations: inferences from 100 Alu insertion polymorphisms. Genome Res 13:1607–1618.
- , , , , , , , , , , , , , , , , , , . 2001. Human hypertension caused by mutations in WNK kinases. Science 293:1107–1112.
- , , , , , , , , . 2003. Molecular pathogenesis of inherited hypertension with hyperkalemia: the Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4. Proc Natl Acad Sci USA 100:680–684.
- , , , , , . 2000. WNK1, a novel mammalian serine/threonine protein kinase lacking the catalytic lysine in subdomain II. J Biol Chem 275:16795–16801.
- , , . 2002. Genome-wide detection of tissue-specific alternative splicing in the human transcriptome. Nucleic Acids Res 30:3366–3754.

1098-1004/asset/HUMU_left.gif?v=1&s=4065e12063da1c0efe3c1a74d4f13c3cd92fba18)
1098-1004/asset/HUMU_right.gif?v=1&s=58026811b6aa5bee5a3d0e0563a705f8b681f34d)
