Insulin resistance is an important risk factor for atherosclerosis. Insulin resistance varies widely within populations, and substantial evidence indicates that much of this variation can be attributed to genetic sources. Visceral adiposity, another important atherosclerosis risk factor, is strongly correlated with insulin resistance, and this trait also appears to be under substantial genetic control. The overall goals of the proposed research project are to: 1) identify the genetic determinants of insulin resistance and visceral adiposity; and 2) determine the extent to which insulin resistance visceral adiposity, and metabolic cardiovascular disease risk factors share common genetic influences. To address these goals, we will enroll 160 families of African-American and Hispanic background who are participating in the Insulin Resistance Atherosclerosis Study (ERAS). Approximately 1280 additional family members will be recruited. Insulin resistance will be measured using the frequently sampled intravenous glucose tolerance test, and visceral adiposity will be measured using computed tomography. A panel of other metabolic cardiovascular disease risk factors will also be assessed. A panel of 370 microsatellite markers will be genotyped from DNA, and a genome-wide scan will be performed to detect chromosomal regions containing loci that influence phenotypic variation. We will then saturate the regions of linkage identified in these analyses with additional markers and will then perform linkage disequilibrium analyses in effort to localize further the putative loci. The organization of this study will be similar to that of IRAS, with three clinical centers, a coordinating center, a central laboratory and a genetic laboratory. This center at the University of Southern California will be responsible for performing and coordinating laboratory measurements, as well as for analysis of insulin sensitivity and other metabolic parameters. This project will contribute substantially to our understanding of the genetic determinants of insulin sensitivity, and consequently to risk of atherosclerosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL060931-03
Application #
6390040
Study Section
Special Emphasis Panel (ZHL1-CSR-R (M1))
Program Officer
Sholinsky, Phyliss
Project Start
1999-08-15
Project End
2003-07-31
Budget Start
2001-08-07
Budget End
2002-07-31
Support Year
3
Fiscal Year
2001
Total Cost
$356,224
Indirect Cost
Name
University of Southern California
Department
Physiology
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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