Abstract

This project will study extended families from the largest """"""""closed population"""""""" in North America (Chicoutimi-Saguenay-Lac St. Jean, Canada). They have identified 99 families from this unique population on the basis of each family having two siblings with both hypertension and dyslipidemia. One of the goals of this project is to obtain DNA, blood pressure, and anthropomorphic measurements in both parents and a total of 400 hypertensive and 400 normotensive 25-55 year old offspring in these families. These investigators also propose to complete extensive inpatient phenotyping in 200 of the younger (25-55) hypertensive and 200 normotensive siblings in these families. Regions of three selected quantitative trait loci found to be in linkage disequilibrium will be mapped with a family-based association haplotype analysis using single nucleotide polymorphisms (SNPs) as genetic markers coupled with a transmission disequilibrium test (TDT). The haplotype regions narrowed in the Canadian families within the area of linkage disequilibrium will be utilized in a case/control study to identify genes in African Americans of Milwaukee using SNPs in positional candidate genes. Both clinical projects will build upon broad based phenotyping data to determine if distinct clusters of traits can be identified to stratify hypertensive subjects for further genetic analysis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL054998-10
Application #
7013116
Study Section
Project Start
2005-02-01
Project End
2006-06-30
Budget Start
2005-02-01
Budget End
2006-06-30
Support Year
10
Fiscal Year
2005
Total Cost
$211,535
Indirect Cost

  Institution

Name
Medical College of Wisconsin
Department
Type
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226

  Publications

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

Showing the most recent 10 out of 82 publications