Abstract

The general objective of the proposed work is the identification and characterization of genetic loci that are involved in the pathogenesis of stroke. The studies will be carried out in an animal model of genetically determined hypertensive cerebrovascular disease, that shares many features with the human disease, viz. the stroke-prone, spontaneously hypertensive rat (SHRSP). Elucidation of disease- associated genes in this model will provide the basis for subsequent studies in humans. The relevance of the proposed studies is evidenced by the importance of stroke as public health issue. As in previous, related work on the genetics of hypertension, both anonymous and sequence-specific markers will be used for the mapping of quantitative trait loci in F2 hybrids derived from cross-breeding SHRSP with stroke- resistant SHR, a strategy that will allow us to avoid blood pressure as a confounding factor in the analysis. Because of the genetic proximity between the two strains, special efforts will be directed towards the development of informative genetic markers. Once a locus is identified, further characterization by both classical genetic (congenics) and molecular (positional cloning) approaches will be pursued.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Modified Research Career Development Award (K04)
Project #
7K04HL003138-02
Application #
2211194
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1994-05-01
Project End
1999-04-30
Budget Start
1995-09-15
Budget End
1996-04-30
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Zee, Robert Y L; Cook, Nancy R; Kim, Chung-Ah et al. (2004) TP53 haplotype-based analysis and incidence of post-angioplasty restenosis. Hum Genet 114:386-90
Zee, Robert Y L; Hegener, Hillary H; Fernandez-Cruz, Arturo et al. (2004) C-reactive protein gene polymorphisms and the incidence of post-angioplasty restenosis. Atherosclerosis 176:393-6
Zee, Robert Y L; Fernandez-Ortiz, Antonio; Macaya, Carlos et al. (2003) IL-1 cluster genes and occurrence of post-percutaneous transluminal coronary angioplasty restenosis: a prospective, angiography-based evaluation. Atherosclerosis 171:259-64
Zee, R Y L; Fernandez-Otiz, A; Macaya, C et al. (2003) Lipid metabolism and occurrence of post-percutaneous transluminal coronary angioplasty restenosis: role of cholesteryl ester transfer protein and paraoxonase/arylesterase. J Thromb Haemost 1:1202-7
Zee, R Y L; Solomon, S D; Ajani, U A et al. (2002) A prospective evaluation of the angiotensin-converting enzyme D/I polymorphism and left ventricular remodeling in the 'Healing and Early Afterload Reducing Therapy' study. Clin Genet 61:21-5
Zee, R Y L; Hoh, J; Cheng, S et al. (2002) Multi-locus interactions predict risk for post-PTCA restenosis: an approach to the genetic analysis of common complex disease. Pharmacogenomics J 2:197-201
Feng, D; Lindpaintner, K; Larson, M G et al. (2001) Platelet glycoprotein IIIa Pl(a) polymorphism, fibrinogen, and platelet aggregability: The Framingham Heart Study. Circulation 104:140-4
Zee, R Y; Fernandez-Ortiz, A; Macaya, C et al. (2001) Ace D/I polymorphism and incidence of post-PTCA restenosis: a prospective, angiography-based evaluation. Hypertension 37:851-5
Niu, T; Struk, B; Lindpaintner, K (2001) Statistical considerations for genome-wide scans: design and application of a novel software package POLYMORPHISM. Hum Hered 52:102-9
Cai, L; Lumsden, A; Guenther, U P et al. (2001) A novel Q378X mutation exists in the transmembrane transporter protein ABCC6 and its pseudogene: implications for mutation analysis in pseudoxanthoma elasticum. J Mol Med 79:536-46

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