Studies are designed to identify genes that cosegregate with hypertension and with phenotypes associated with hypertension (""""""""hypertension associated phenotypes"""""""") in a genetically isolated population with traditionally large families residing in Chicoutimi Saguenay Lac St. Jean, Canada. A genome-wide search and a candidate gene approach will be used and a sib-pair analysis will be carried out using 200 sibs to define hypertension susceptibility loci. We will subdivide the population to further reduce the genetic heterogeneity by including only sib pairs who exhibit both hypertension and hypercholesterolemia. Extensive phenotyping of 200 of these sibs will be carried out to determine loci that influence blood pressure and alterations of physiological functions that may contribute to hypertension. Phenotypic studies will evaluate renal function, renal and peripheral vascular reactivity, insulin sensitivity, and ion transport in erythrocytes. The general linkage analysis will be refined by determining mutations that exist in linkage disequilibrium. Inheritance by descent (IBD) will be determined by studying additional sib pairs from the large family pedigrees (sibs who belong to a family with at least 3 living generations and at least 5 members in 1 generation) to re-analyze mapped phenotypes for their segregation with hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL054998-03
Application #
6273098
Study Section
Project Start
1998-02-01
Project End
1999-01-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Type
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Cowley Jr, Allen W; Abe, Michiaki; Mori, Takefumi et al. (2015) Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension. Am J Physiol Renal Physiol 308:F179-97
Kidambi, Srividya; Ghosh, Soumitra; Kotchen, Jane M et al. (2012) Non-replication study of a genome-wide association study for hypertension and blood pressure in African Americans. BMC Med Genet 13:27
Nikpay, Majid; Seda, Ondrej; Tremblay, Johanne et al. (2012) Genetic mapping of habitual substance use, obesity-related traits, responses to mental and physical stress, and heart rate and blood pressure measurements reveals shared genes that are overrepresented in the neural synapse. Hypertens Res 35:585-91
Shimoyama, Mary; Smith, Jennifer R; Hayman, G Thomas et al. (2012) Model organism databases in behavioral neuroscience. Int Rev Neurobiol 104:25-46
Stekiel, Thomas A; Contney, Stephen J; Roman, Richard J et al. (2011) Pharmacogenomic strain differences in cardiovascular sensitivity to propofol. Anesthesiology 115:1192-200
Orlov, Sergei N; Gossard, Francis; Pausova, Zdenka et al. (2010) Decreased NKCC1 activity in erythrocytes from African Americans with hypertension and dyslipidemia. Am J Hypertens 23:321-6
Shao, Haifeng; Sinasac, David S; Burrage, Lindsay C et al. (2010) Analyzing complex traits with congenic strains. Mamm Genome 21:276-86
Hong, Xiumei; Tsai, Hui-Ju; Liu, Xin et al. (2008) A large-scale genome-wide linkage analysis to map loci linked to stature in Chinese population. J Clin Endocrinol Metab 93:4511-8
Mattson, David L; Dwinell, Melinda R; Greene, Andrew S et al. (2008) Chromosome substitution reveals the genetic basis of Dahl salt-sensitive hypertension and renal disease. Am J Physiol Renal Physiol 295:F837-42
Mori, Takefumi; Polichnowski, Aaron; Glocka, Padden et al. (2008) High perfusion pressure accelerates renal injury in salt-sensitive hypertension. J Am Soc Nephrol 19:1472-82

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