SODIUM TRANSPORT--GENETICS &HYPERTENSION

Project: Research project

Project Details

Description

Essential hypertension (EHYT) is a common chronic disease contributing
to morbidity, morality, and cost of health care. This renewal
application is a continuation of our work to understand the genetic
basis of interindividual variation in risk of EHYT in the population at
large using the Rochester Family Heart Study (RFHS). This resource
involves 4053 members of 560 multigeneration pedigrees ascertained
without regard to health status who have undergone a physical
examination and provided blood for laboratory studies. This resource is
being utilized to address three major questions: 1) Which intermediate
biochemical, physiological, and anthropomorphic traits predict blood
pressure (BP) and contribute to the pathogenesis of EHYT? 2) Does
allelic variation in one or more genes have large effects on any of
these intermediate traits? 3) Does information about allelic variation
improve prediction of risk of EHYT beyond what is provided by measure of
the intermediate traits? AIMS 1-4 of this application focus on the
first question, AIM 5 on the second, and AIM 6 on the third.

AIM 1 will use 120 RFHS pedigrees to determine whether the single
genetic or environmental factor identified as having a large effect on
erythrocyte (RBC) sodium-lithium countertransport (NA-Li CNT) has a
large impact on RBC and/or lymphocyte sodium-hydrogen exchange activity.
AIM 2 seeks to determine whether measures of renal hemodynamic non-
modulation (on high salt diet), renal tubular sodium (Na+) reabsorption,
insulin resistance, heightened sympathetic nervous system activity, or
alterations in lipid metabolism explain the statistical association
between elevated Na-Li CNT and development of EHYT in these pedigrees.
AIM 3 will establish the extent to which measures of the 24-hour
ambulatory BP profile can be explained by traits studied in AIM 1 and 2.
AIM 4 will consider 800 unrelated members of 294 RFHS pedigrees to
determine if RBC Na-K ATPase pump, sodium-potassium cotransport,
intracellular Na+, or plasma levels of atrial natriuretic peptide
contribute to prediction of EHYT. AIM 5 will use all 2049 participants
of these pedigrees to establish whether one or more single genes have
major effects on traits identified as predictors of EHYT in AIM 4. AIM
6 will estimate the relative contribution of genes identified in AIM 5
to the prediction of EHYT.
StatusFinished
Effective start/end date4/1/843/31/97

ASJC

  • Medicine(all)