Rare mutations in SLC12A1 and SLC12A3 protect against hypertension by reducing the activity of renal salt cotransporters

Acuña, RocíoRocíoAcuñaMartínez-de-la-Maza, LiliaLiliaMartínez-de-la-MazaPonce-Coria, JoséJoséPonce-CoriaVázquez, NormaNormaVázquezOrtal-Vite, PenélopePenélopeOrtal-VitePacheco Álvarez, DianaDianaPacheco ÁlvarezBobadilla, Norma A.Norma A.BobadillaGamba, GerardoGerardoGamba2023-01-262023-01-262011https://scripta.up.edu.mx/handle/20.500.12552/240210.1097/HJH.0b013e328341d0fdObjectives: Screening for variants in SLC12A1 and SLC12A3 genes, encoding the renal Na:Cl (NCC) and Na:K:2Cl (NKCC2) cotransporters, respectively, in 3125 members of the Framingham Heart Study (FHS) revealed that carrying a rare mutation in one of these genes was associated with a significant reduction in blood pressure, in the risk of arterial hypertension, and of death due to cardiovascular disease. Because near 60% of the rare mutations identified have not been related to Bartter's or Gitelman's disease, the consequence of such mutations on cotransporter activity is unknown. Methods: We used the heterologous expression system of Xenopus laevis oocytes, microinjected with wild-type or mutant NCC or NKCC2 cRNAs, to examine the effect of these inferred NCC and NKCC2 mutations on the cotransporters' functional properties. Cotransporter activity was defined as the diuretic-sensitive radioactive tracer uptake and response to known modulators was assessed. © Journal of HypertensionenRare mutations in SLC12A1 and SLC12A3 protect against hypertension by reducing the activity of renal salt cotransportersResource Types::text::journal::journal article