This is continuing study of hypertensive subjects, their nuclear families and extended pedigrees. The long term goal is to understand the pathophysiology of different types of essential hypertension (HBP). Defining the specific causes and cardiovascular disease risks of different types of HBP will lead to better methods for detection, assessment, treatment and prevention of HBP. (e.g. some may need drug Rx more than others, etc.) An informative battery of special cation tests, special blood pressures, other pertinent variables, and a detailed medical family history (FHx) have been collected on 2548 subjects in 98 extended pedigrees in Utah. Special cation tests appear to be largely genetically determined and involved in the pathophysiology of HBP. Cation tests under study include: Na-Li Countertransport; Li-K Cotransport; intracellular Na,K,Mg; Na-K ATPase pump activity and binding sites; and plasma levels of Na, K, Mg, ionized Ca and digoxin-like pump inhibitor. Special BP's include sitting, standing, lying, tilting, and BP during venipuncture, mental arithmetic, bicycle exercise, isometric handgrip exercise, and 24 hour ambulatory monitoring. Other variables informative in preliminary analyses include detailed anthropometics, blood lipids, stress and exercise questionnaires, urine electrolytes, plasma renin activity, urinary kallikrein, and detailed FHx of HBP, CHD and CYA. Five proposed specivic aims include: 1. Continue statistical and pedigree analyses of data already collected on 2548 subjects. 2. Perform the same tests on 600 new, population-based HBP subjects on drug Rx and again 4 months after interruption of drug Rx to obtain unconfounded values of biochemical and BP tests. 3. Test for specific subtypes of HBP among these 600 subjects using individual variables and multivariate combinations of variables. Characterize specific HBP syndromes. 4. Screen 300 nuclear families (N=1200) to test for familiality of subtype indicators and to identify those HBP subtype indicator variables deserving detailed pedigree analysis. 5. Study 1000 sequentially sampled persons in 40 extended pedigrees to test for major genes, DNA probe linkage, and gene-environment interactions as determinants of specific types of hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL024855-07
Application #
3337838
Study Section
(SSS)
Project Start
1980-02-01
Project End
1991-01-31
Budget Start
1986-02-01
Budget End
1987-01-31
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Shirts, Brian H; Howard, Michael T; Hasstedt, Sandra J et al. (2012) Vitamin D dependent effects of APOA5 polymorphisms on HDL cholesterol. Atherosclerosis 222:167-74
B├╝sst, Cara J; Bloomer, Lisa D S; Scurrah, Katrina J et al. (2011) The epithelial sodium channel ?-subunit gene and blood pressure: family based association, renal gene expression, and physiological analyses. Hypertension 58:1073-8
Shirts, Brian H; Hasstedt, Sandra J; Hopkins, Paul N et al. (2011) Evaluation of the gene-age interactions in HDL cholesterol, LDL cholesterol, and triglyceride levels: the impact of the SORT1 polymorphism on LDL cholesterol levels is age dependent. Atherosclerosis 217:139-41
Hasstedt, Sandra J; Xin, Yuanpei; Hopkins, Paul N et al. (2010) Two-dimensional, sex-specific autosomal linkage scan of the number of sodium pump sites. J Hypertens 28:740-7
Hunt, Steven C; Xin, Yuanpei; Wu, Lily L et al. (2006) Sodium bicarbonate cotransporter polymorphisms are associated with baseline and 10-year follow-up blood pressures. Hypertension 47:532-6
Johnson, Jenny; Giles, Rebecca T; Larsen, Ladene et al. (2005) Utah's Family High Risk Program: bridging the gap between genomics and public health. Prev Chronic Dis 2:A24
Coon, Hilary; Xin, Yuanpei; Hopkins, Paul N et al. (2005) Upstream stimulatory factor 1 associated with familial combined hyperlipidemia, LDL cholesterol, and triglycerides. Hum Genet 117:444-51
Hasstedt, Sandra J; Camp, Nicola J; Hopkins, Paul N et al. (2004) Model-fitting and linkage analysis of sodium-lithium countertransport. Eur J Hum Genet 12:1055-61
Hunt, Steven C; Coon, Hilary; Hasstedt, Sandra J et al. (2004) Linkage of serum creatinine and glomerular filtration rate to chromosome 2 in Utah pedigrees. Am J Hypertens 17:511-5
Camp, Nicola J; Hopkins, Paul N; Hasstedt, Sandra J et al. (2003) Genome-wide multipoint parametric linkage analysis of pulse pressure in large, extended utah pedigrees. Hypertension 42:322-8

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