Molecular & Clinical Evaluation of Low HDL Syndromes
Molecular & Clinical Evaluation of Low HDL Syndromes
To study the genetic cause of low HDL-C, a risk factor for premature atherosclerotic vascular
 disease in patients with normal total cholesterol. The focus is primarily on the
 identification of a single mutation, as has been demonstrated in one family.
BACKGROUND:

 Low levels of high density lipoprotein cholesterol (HDL-C) have been found to be associated
 with an increased risk for coronary artery disease (CAD). However, the genetic basis for this
 association is not well understood and the clinical implications of this association have not
 been extensively addressed. The study, in seeking to elucidate the genetic basis for low
 HDL-C and examine the clinical implications of low HDL-C, focuses upon an important research
 topic.

 DESIGN NARRATIVE:

 Specific aims of the study include: 1) Collection and characterization of plasma and DNA from
 probands with very low HDL-C. Linkage analysis will be performed using highly polymorphic
 markers within or near HDL-C candidate genes. The hypothesis to be tested is that polymorphic
 microsatellites segregate with the low HDL-C phenotype.

 2) Further genetic characterization of families evidence of linkage to specific HDL-C
 candidate genes identified in Specific Aim 1. The hypothesis to be tested is that structural
 variants in HDL-C candidates are responsible for low HDL-C.

 3) Evaluate the physiologic significance of novel genomic variants identified in Specific Aim
 2. The hypothesis to be tested is that structural variants will affect expression of the gene
 product.

 4) Examine early atherosclerosis in low HDL-C syndromes. The hypothesis to be tested is that
 increased carotid intima-medial thickness is prevalent with isolated low HDL-C.
No eligibility criteria