title: A WNK4 gene variant relates to osteoporosis and not to hypertension in the Portuguese population.
abstract: Germline mutations in the WNK4 gene originate Gordon syndrome or pseudohypoaldosteronism type II, a familial form of hypertension with hyperkalemia and hypercalciuria. In order to elucidate the contribution of WNK4 genetic variants to hypertension and/or osteoporosis, we analyzed 271 control individuals and a cohort of 448 hypertensive and 372 osteoporosis patients from the Portuguese population. Ten genetic variants were detected in 4.3% of the population under study, none of which revealed any significant association to the hypertension phenotype. In contrast, a rare missense alteration within exon 17 in a highly conserved arginine residue showed a possible tendency for association to the osteoporosis group. Our data suggest that WNK4 polymorphism rs56116165 is a rare allelic variant in a candidate gene with a biological function in renal calcium homeostasis that may contribute to a genetic predisposition to osteoporosis.
authors.affiliation: Departamento de Genética, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Mendes
authors.forename: Mário Rui
authors.initials: MR
authors.lastname: Mascarenhas
authors.forename: Sónia
authors.initials: S
authors.lastname: Matos
authors.forename: Inês
authors.initials: I
authors.lastname: Sousa
authors.forename: Joana
authors.initials: J
authors.lastname: Ferreira
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Barbosa
authors.forename: Manuel
authors.initials: M
authors.lastname: Bicho
authors.forename: Peter
authors.initials: P
authors.lastname: Jordan
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D007438:Introns; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010024:Osteoporosis / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; C433806:WNK4 protein, human