Disease relevance of Add1

• In previous studies, an association has been found between the alpha-adducin Gly460Trp polymorphism and salt-sensitive hypertension [1].
• Association between the alpha-adducin Gly460Trp polymorphism and systolic blood pressure in familial combined hyperlipidemia [1].

High impact information on Add1

• We have isolated another PKC binding protein partial cDNA (clone 45) from a rat fibroblast library with substantial homology to alpha-adducin [2].
• Antisera raised against this expressed sequence recognized a protein of 120 kDa, the reported size of alpha-adducin, on immunoblots of renal proximal tubule epithelial cell extracts [2].
• Phorbol esters stimulated alpha-adducin phosphorylation to a greater extent in primary cells than in oncogene-altered cells, possibly because of the already high basal levels of phosphorylation in those cells [3].
• Effect of Add1 gene transfer on blood pressure in reciprocal congenic strains of Milan rats [4].
• Immuno-electron microscopic analysis of peroxidase stained sections of the hippocampus and the cerebellum revealed that alpha-adducin is localized at distinct sub-cellular structures [5].

Chemical compound and disease context of Add1

• In this short editorial review, we summarize the recent experimental, clinical and epidemiological evidence that contributed to our understanding of the pathogenetic mechanisms that lead to hypertension associated with the alpha-adducin Gly460Trp polymorphism and its interaction with ouabain [6].
• In rats and humans, mutation of the alpha-adducin subunit leads to the stimulation of the sodium (Na(+)), potassium (K(+))-adenosine triphosphate (ATP)-ase activity in renal tubular cells, increased renal Na(+) reabsorption, and, subsequently, hypertension [6].

Biological context of Add1

• We found evidence that QTLs affected systolic blood pressure (SBP) measured at the carotid (direct SBP) on rat chromosome 1 with a logarithm of the odds (LOD) score peak of 3.3 on D1Rat121 and on rat chromosome 14 on Add1 locus (LOD=3.2) [7].

Anatomical context of Add1

• Alpha-adducin is found to be highly enriched in regions with high synapse densities of the hippocampus, corpus striatum, cerebral cortex and cerebellum [5].

Associations of Add1 with chemical compounds

• Plasma ouabain levels increase with the number of copies of the mutated alpha-adducin allele [6].

Other interactions of Add1

• In the present study, a genomewide search with 264 informative markers was undertaken in 251 (Milan hypertensive strain x Milan normotensive strain) F2 rats to further investigate the contribution of the adducin gene family (Add1, Add2, and Add3) and to identify novel quantitative trait loci (QTLs) that affect blood pressure [7].

References