Work of the SCOR has demonstrated the key role of inherited variation in renal salt handling in blood pressure variation in humans. These findings from rate Mendelian diseases raise the question of whether more common variants in genes of this same pathway alter blood pressure in the general population. This project investigates the causes of inherited variation in blood pressure, end-stage renal disease and left ventricular hypertrophy. Study populations are 4100 members of the Framingham Heart Study and multiplex kindreds with end-stage renal disease recruited from the GAMBRO dialysis centers.
Specific Aim 1 will investigate the impact of single nucleotide polymorphisms in genes in which mutations cause inherited forms of high or low blood pressure on blood pressure and LVH in 4000 subjects from the Framingham Heart Study. This Study has substantial power to detect even modest effects imparted by these variants.
Specific Aim 2 will work toward the positional cloning of a blood pressure locus on chromosome 17 that demonstrated a lod score of 4.7 for linkage to systolic blood pressure in families from Framingham Study.
| Zhang, Junhui; Geller, David S (2008) Helix 3-helix 5 interactions in steroid hormone receptor function. J Steroid Biochem Mol Biol 109:279-85 |
| Mani, Arya; Radhakrishnan, Jayaram; Wang, He et al. (2007) LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science 315:1278-82 |
| Alvarez de la Rosa, Diego; Gimenez, Ignacio; Forbush, Biff et al. (2006) SGK1 activates Na+-K+-ATPase in amphibian renal epithelial cells. Am J Physiol Cell Physiol 290:C492-8 |
| Zhang, Junhui; Tsai, Francis T F; Geller, David S (2006) Differential interaction of RU486 with the progesterone and glucocorticoid receptors. J Mol Endocrinol 37:163-73 |
| Zhang, Junhui; Simisky, Jessica; Tsai, Francis T F et al. (2005) A critical role of helix 3-helix 5 interaction in steroid hormone receptor function. Proc Natl Acad Sci U S A 102:2707-12 |
| Geller, David S (2005) Mineralocorticoid resistance. Clin Endocrinol (Oxf) 62:513-20 |
| Wilson, Frederick H; Hariri, Ali; Farhi, Anita et al. (2004) A cluster of metabolic defects caused by mutation in a mitochondrial tRNA. Science 306:1190-4 |
| Coric, Tatjana; Hernandez, Nelmary; Alvarez de la Rosa, Diego et al. (2004) Expression of ENaC and serum- and glucocorticoid-induced kinase 1 in the rat intestinal epithelium. Am J Physiol Gastrointest Liver Physiol 286:G663-70 |
| Geller, David S (2004) A genetic predisposition to hypertension? Hypertension 44:27-8 |
| Francis, Jean; Zhang, Junhui; Farhi, Anita et al. (2004) A novel SGLT2 mutation in a patient with autosomal recessive renal glucosuria. Nephrol Dial Transplant 19:2893-5 |
Showing the most recent 10 out of 21 publications
