Role of Alström syndrome 1 in the regulation of blood pressure and renal function

• DOI: 10.1172/jci.insight.95076
• Publication Date: 2018-11-01T15:01:23Z
• Authors: Ankita Bachhawat ...; Paulo S. Caceres; Keyona N. King-Me...; Tang-Dong Liao; Indrani Datta; Dipak Maskey; Jürgen K. Naggert; Mariela Mendez; William H. Beierw...; Pablo A. Ortiz
• Keywords: Genome-wide Association Study; Candidate gene

Elevated blood pressure (BP) and renal dysfunction are complex traits representing major global health problems. Single nucleotide polymorphisms identified by genome-wide association studies have the Alström syndrome 1 (ALMS1) gene locus to render susceptibility for dysfunction, hypertension, chronic kidney disease (CKD). Mutations in ALMS1 humans causes syndrome, characterized progressive metabolic alterations including hypertension CKD. Despite compelling genetic evidence, underlying biological mechanism which mutations lead above-mentioned pathophysiology is not understood. We modeled this effect a KO rat model showed that deletion leads hypertension. demonstrate link between involves activation of Na+/K+/2Cl- cotransporter NKCC2, mediated regulation its endocytosis. Our findings establish CKD, expression through role salt-reabsorbing tubular segment kidney. These data point as potentially novel involved BP function regulation.