Essential hypertension [EHYT] reaches epidemic proportions among adults and is a significant risk factor for premature coronary artery disease [CAD] and stroke. The overall objective of this revised proposal is to localize individual genes, called blood pressure quantitative train genes [BPQTGs], which influence blood pressure levels in the population-at- large, and to determine if these genes are able to predict the occurrence of EHYT or CAD. This project will make use of previously collected DNA and clinical data from members of 573 randomly-ascertained multigeneration pedigrees from the Rochester Family Heart Study. Two complementary research strategies will be used to located BPQTGs.
Aim 1 will use robust sibling pair linkage methods, parental marker data, and office BP levels measured on 1,376 full sibling pairs to localize BPQTGs to regions of the human genome marked by highly polymorphic tandem repeat loci in or very near to 59 genes involved in BP regulation. These genes were selected based on their involvement in the renin/angiotensin system, ion transport, cardiac physiology, biometabolism of neurotransmitters, or carbohydrate and lipid metabolism. At each gene, a highly polymorphic tandem repeat marker locus has already been identified.
Aim 2 will use methods of association analysis for related individuals and office BP levels measured on 587 full sibships to localize BPQTGs to regions of the human genome marked by the 59 candidate BPQTGs.
Aim 3 will determine if variation in these BPQTGs improves the ability to predict differences in BP levels in a sample of 1,166 unrelated normotensive adults of EHYT status in a sample of 1,160 unrelated grandparents beyond that provided by established predictors.
Aim 4 will determine if variation in these BPQTGs improves the ability to predict symptomatic or asymptomatic CAD status beyond that provided by established predictors including BP and EHYT.
Aims 3 and 4 will also ask whether the predictive relationship of the traditional risk factors to BP, EHYT, or CAD is different among genotypes at these BPQTGs. The research proposed here to localize BPQTGs represents an initial step toward applying DNA information to early identification of at-risk individuals and understanding the complex relationship between BP, EHYT and CAD.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL051021-04
Application #
2430721
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1994-07-08
Project End
1999-05-31
Budget Start
1997-06-06
Budget End
1998-05-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Genetics
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Non, Amy L; Gravlee, Clarence C; Mulligan, Connie J (2012) Education, genetic ancestry, and blood pressure in African Americans and Whites. Am J Public Health 102:1559-65
Dmitrieva, Renata I; Hinojos, Cruz A; Grove, Megan L et al. (2009) Genome-wide identification of allelic expression in hypertensive rats. Circ Cardiovasc Genet 2:106-15
Montasser, May E; Shimmin, Lawrence C; Hanis, Craig L et al. (2009) Gene by smoking interaction in hypertension: identification of a major quantitative trait locus on chromosome 15q for systolic blood pressure in Mexican-Americans. J Hypertens 27:491-501
Bressler, Jan; Fornage, Myriam; Hanis, Craig L et al. (2009) The INSIG2 rs7566605 genetic variant does not play a major role in obesity in a sample of 24,722 individuals from four cohorts. BMC Med Genet 10:56
Chung, Charles C; Shimmin, Lawrence; Natarajan, Sivamani et al. (2009) Glucocorticoid receptor gene variant in the 3' untranslated region is associated with multiple measures of blood pressure. J Clin Endocrinol Metab 94:268-76
Klos, Kathy; Shimmin, Lawrence; Ballantyne, Christie et al. (2008) APOE/C1/C4/C2 hepatic control region polymorphism influences plasma apoE and LDL cholesterol levels. Hum Mol Genet 17:2039-46
Leduc, Magalie S; Shimmin, Lawrence C; Klos, Kathy L E et al. (2008) Comprehensive evaluation of apolipoprotein H gene (APOH) variation identifies novel associations with measures of lipid metabolism in GENOA. J Lipid Res 49:2648-56
Dmitrieva, Renata I; Hinojos, Cruz A; Boerwinkle, Eric et al. (2008) Hepatocyte nuclear factor 1 and hypertensive nephropathy. Hypertension 51:1583-9
Gu, C Charles; Yu, Kai; Boerwinkle, Eric (2007) Measuring marker information content by the ambiguity of block boundaries observed in dense SNP data. Ann Hum Genet 71:127-40
Saunders, Catherine L; Chiodini, Benedetta D; Sham, Pak et al. (2007) Meta-analysis of genome-wide linkage studies in BMI and obesity. Obesity (Silver Spring) 15:2263-75

Showing the most recent 10 out of 47 publications