This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Circulating levels of LDL constitute the major risk factor for coronary artery disease--the largest cause of death in America today. Plasma levels of LDL-cholesterol vary from individual to individual. While 50% of this variation is attributable to diet, exercise and other factors, 50% of this variation is attributable to genetics. PCSK9 is a secreted serine protease that plays a critical role in cholesterol homeostasis.Select sequence variations in PCSK9 that result in low plasma LDL-cholesterol have been identified in family DHS20 (study #1287-355). So far, family members with no affected alleles, one affected allele and both affected alleles have been identified. While plasma level of LDL-cholesterol vary according to the number of affected alleles, no additional differences in physiologic parameters have been observed. To ensure that the absence of PCSK9 does not confer additional physiologic change beyond its effect on plasma LDL-cholesterol, we wish to perform a comprehensive clinical evaluation of subjects with absent, low and normal levels of plasma PCSK9. Ultimately the goal of the project is to determine if the absence of circulating PCSK9 is related to clinical pathology within and beyond the organs in which PCSK9 is expressed.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000633-35
Application #
7606356
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2007-04-01
Project End
2007-09-16
Budget Start
2007-04-01
Budget End
2007-09-16
Support Year
35
Fiscal Year
2007
Total Cost
$51
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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