Genetic Determinants:Low HDL, High Triglycerides, Obesity

This study has been completed.
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI) Identifier:
First received: November 14, 2002
Last updated: June 23, 2005
Last verified: January 2005
To conduct genetic studies of the metabolic syndrome characterized by very low levels of high density lipoprotein cholesterol (HDL-C), hypertriglyceridemia, and obesity.

Cardiovascular Diseases
Heart Diseases
Metabolic Syndrome X

Study Type: Observational
Study Design: Observational Model: Natural History

Resource links provided by NLM:

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Study Start Date: April 2002
Estimated Study Completion Date: March 2004
Detailed Description:


Over the past 10 years, extensive studies have been conducted in Turkey to determine the risk factors for heart disease. Studies involving approximately 10,000 Turkish men and women from six different regions of Turkey have established that this population is unique in several ways. The Turks have the lowest plasma levels of high density lipoprotein cholesterol (HDL-C) of almost any population in the world (75 percent of the men and 50 percent of the women have HDL-C levels <40 mg/dl). The mean HDL-C levels are 10-15 mg/dl lower than those in Western European or American populations. In addition, Turks, especially Turkish women, have a tendency toward obesity [38.8 percent of the women have body mass index (BMI) >30 kg/M2], and both men and women have a tendency toward hypertriglyceridemia. The low HDL-C, however, is independent of obesity or hypertriglyceridemia. Samples from this well-characterized population provide a unique opportunity to explore the genetic determinants associated with the high prevalence of low HDL-C, hypertriglyceridemia, and obesity (characteristics of the metabolic syndrome).

The study was in response to a Request for Applications entitled "NHLBI Innovative Research Grant Program" released in July, 2001. The purpose of the initiative was to support new approaches to heart, lung, and blood diseases and sleep disorders that used existing data sets or existing biological specimen collections whether obtained through National Heart, Lung, and Blood Institute support or not.


The study analyzed DNA from frozen blood samples to investigate new candidate gene targets that provided insights into the abnormalities characterizing this population of Turks. The samples and extensive biodata were available on all 10,000 participants. In Specific Aim 1, the investigators identified polymorphisms in acyl CoA:diacylglycerol acyltranferase (DGAT)- I and -2 and in ATP-binding cassette A I (ABCA I) genes that were associated with differences in BMI, HDL-C, and triglyceride concentration, and other parameters such as blood pressure. These studies focussed significantly on promoter and coding sequence polymorphisms in DGAT-I and -2 and ABCAL In Specific Aim 2, the investigators determined whether the polymorphisms had functional significance by using a luciferase reporter system to determine expression of polymorphic forms of DGAT and ABCAI, a cholesterol efflux measurement to determine the functional significance of ABCAI coding sequence polymorphic sites, and a triglyceride synthesis assay to determine the functional significance of DGAT-I and -2 polymorphic sites. The polymorphic site association studies were performed on DNA samples from three subgroups of Turks: (a) individuals likely to have the metabolic syndrome, (b) individuals with isolated low HDL-C (normal triglycerides), and (c) normolipidemic unaffected controls.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
No eligibility criteria
  Contacts and Locations
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Please refer to this study by its identifier: NCT00049881

Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigator: Robert Mahley J. David Gladstone Institutes
  More Information

No publications provided Identifier: NCT00049881     History of Changes
Other Study ID Numbers: 1202
Study First Received: November 14, 2002
Last Updated: June 23, 2005
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Cardiovascular Diseases
Metabolic Syndrome X
Arterial Occlusive Diseases
Glucose Metabolism Disorders
Insulin Resistance
Lipid Metabolism Disorders
Metabolic Diseases
Vascular Diseases processed this record on December 01, 2015