Novel polymorphic AluYb8 insertion in the WNK1 gene is associated with blood pressure variation in Europeans.
Bottom Line: Meta-analysis across three European sample sets (n = 3,494; HYPEST, Estonians; BRIGHT, the British; CADCZ, Czech) detected significant association of the WNK1 AluYb8 insertion with blood pressure (BP; systolic BP, P = 4.03 × 10(-3) , effect 1.12; diastolic BP, P = 1.21 × 10(-2) , effect 0.67).Gender-stratified analysis revealed that this effect might be female-specific (n = 2,088; SBP, P = 1.99 × 10(-3) , effect 1.59; DBP P = 3.64 × 10(-4) , effect 1.23; resistant to Bonferroni correction), whereas no statistical support was identified for the association with male BP (n = 1,406).In leucocytes, the expressional proportions of the full-length WNK1 transcript and the splice-form skipping exon 11 were significantly shifted in AluYb8 carriers compared to noncarriers.
Affiliation: Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.Show MeSH
Related in: MedlinePlus
Mentions: For large-scale genotyping of WNK1 AluYb8 in humans PCR followed by standard agarose gel electrophoresis was used. The primer design (WNK1_Alu_F: 5′-GGGTAACCAACCCTTGAAGTAGG-3′; WNK1_Alu_R: 5′-GGGTACTTCTCAAGTGATTAGGAGGA-3′) was carried out using the Web-based program Primer3 [Rozen and Skaletsky, 2000]. Quality control of the genotyping by agarose gel electrophoresis was assured by including previously resequenced positive controls representing alternative genotype carriers on each gel: wild-type (PCR product 353 bp); heterozygous (PCR products 353 and 660 bp) and homozygous (PCR product 660 bp) individuals for the AluYb8 insertion (Fig. 1; Supp. Figs. S1 and S2). The distribution of the WNK1 AluYb8 insertion was studied in six European (Estonians, n = 100; Czech, n = 50; CEPH, n = 30; the Basque, n = 50; Catalans, n = 41; Spanish Gypsies, n = 50), four Asian (Koreans, n = 43; Chinese Han, n = 25; Tatars, n = 47; Bashkir, n = 47), and eight African populations (Tunisians, n = 48; Algerians, n = 48; Moroccans, n = 84; Mandenkalu, n = 24; Saharawi, n = 50; Gabon Bantus, n = 50; Gabon Pygmies, n = 50; Tanzanians, n = 17).
Affiliation: Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.