title: Variants in striatin gene are associated with salt-sensitive blood pressure in mice and humans.
abstract: Striatin is a novel protein that interacts with steroid receptors and modifies rapid, nongenomic activity in vitro. We tested the hypothesis that striatin would in turn affect mineralocorticoid receptor function and consequently sodium, water, and blood pressure homeostasis in an animal model. We evaluated salt sensitivity of blood pressure in novel striatin heterozygote knockout mice. Compared with wild type, striatin heterozygote exhibited a significant increase in blood pressure when sodium intake was increased from restricted (0.03%) to liberal (1.6%) sodium. Furthermore, renal expression of mineralocorticoid receptor and its genomic downstream targets serum/glucocorticoid-regulated kinase 1, and epithelial sodium channel was increased in striatin heterozygote versus wild-type mice on liberal sodium intake while the pAkt/Akt ratio, readout of mineralocorticoid receptor's rapid, nongenomic pathway, was reduced. To determine the potential clinical relevance of these findings, we tested the association between single nucleotide polymorphic variants of striatin gene and salt sensitivity of blood pressure in 366 white hypertensive subjects. HapMap-derived tagging single nucleotide polymorphisms identified an association of rs2540923 with salt sensitivity of blood pressure (odds ratio, 6.25; 95% confidence interval, 1.7-20; P=0.01). These data provide the first in vivo evidence in humans and rodents that associates striatin with markers of mineralocorticoid receptor activity. The data also support the hypothesis that the rapid, nongenomic mineralocorticoid receptor pathway (mediated via striatin) has a role in modulating the interaction between salt intake and blood pressure.
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115, USA.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Garza
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115, USA.
authors.forename: Chevon M
authors.initials: CM
authors.lastname: Rariy
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115, USA.
authors.forename: Bei
authors.initials: B
authors.lastname: Sun
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Williams
authors.affiliation: Channing Department of Network Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lasky-Su
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115, USA.|Department of Endocrinology, School Of Medicine, Pontificia Universidad Catolica De Chile, Santiago 8330074, Chile.
authors.forename: Rene
authors.initials: R
authors.lastname: Baudrand
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115, USA.
authors.forename: Tham
authors.initials: T
authors.lastname: Yao
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115, USA.
authors.forename: Burhanuddin
authors.initials: B
authors.lastname: Moize
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115, USA.
authors.forename: Wan M
authors.initials: WM
authors.lastname: Hafiz
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115, USA.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Romero
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115, USA.
authors.forename: Gail K
authors.initials: GK
authors.lastname: Adler
authors.affiliation: Division of Internal Medicine & Nephrology and School of Internal Medicine, University of L'Aquila - San Salvatore Hospital, V.le San Salvatore - Delta 6 Building, Coppito 67100 AQ, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ferri
authors.affiliation: Division of Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, UT 84108.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115, USA.
authors.forename: Luminita H
authors.initials: LH
authors.lastname: Pojoga
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. Boston, MA 02115, USA.
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Williams
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D015153:Blotting, Western; D002148:Calmodulin-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D012982:Sodium, Dietary / Q000009:adverse effects*
chemical_list: D002148:Calmodulin-Binding Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C491925:STRN protein, human; D012982:Sodium, Dietary; C491924:Strn protein, mouse
keywords: blood pressure; polymorphism, single nucleotide; striatin protein, mouse