Ignite Creation Date:
2024-05-05 @ 9:36 AM
Last Modification Date:
2024-10-26 @ 9:04 AM
Study NCT ID:
NCT00005203
Status:
COMPLETED
Last Update Posted:
2016-02-10
First Post:
2000-05-25
Brief Title:
Genetics of Low Density Lipoprotein Subclasses in Hypercholesterolemia
Sponsor:
University of Washington
Organization:
University of Washington
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2004-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To perform genetic studies of low density lipoprotein LDL subclasses in 160 families in whom the probands had metabolically defined hypercholesterolemia
Detailed Description:
BACKGROUND
Low density lipoprotein cholesterol has been convincingly established as a major coronary heart disease risk factor by many epidemiologic studies clinical trials and experimental studies A strong inverse association exists between high density lipoprotein cholesterol and coronary heart disease However the status of very low density lipoprotein VLDL cholesterol and plasma triglyceride levels as independent risk factors for cardiovascular disease is less clear Case control studies have shown a positive association between coronary heart disease and plasma levels of apoprotein B the major protein on LDL particles and an inverse relationship with apoprotein AI the primary protein constituent of HDL particles In fact it has been proposed that plasma levels of the apoproteins may be stronger risk factors than lipid levels Thus understanding the mechanisms underlying variations in both lipoprotein and apoprotein levels among individuals is essential to elucidating the etiology of coronary heart disease in the general population
Cardiovascular disease is also known to cluster in families and this may be related to the clustering of lipid and lipoprotein levels among family members A review suggested that the familial aggregation of heart disease may be primarily a reflection of the familial aggregation of known risk factors including cholesterol levels The work of Goldstein and Brown on familial hypercholesterolemia demonstrated that genetic control of lipoprotein metabolism can play a causative role in the development of atherosclerosis However familial hypercholesterolemia is a relatively rare disorder the prevalence of heterozygotes is estimated to be 1 in 500 homozygotes 1 in a million In 1987 little was understood about more common genetic contributions to lipid and lipoprotein abnormalities leading to the familial aggregation of coronary heart disease
DESIGN NARRATIVE
The design was that of a cross-sectional family study The recruitment and screening of probands were conducted over a four-year period at the University of Texas at Dallas under separate funding The recruitment and screening of first-degree relatives were carried out at Berkeley Blood samples were obtained from relatives for LDL subclass analysis and for lipid and apoprotein determination An interview was conducted to obtain demographic information and information on behavioral and environmental risk factors such as smoking exercise and diet The data were used to determine whether LDL subclasses were genetically controlled in families with hypercholesterolemia due to overproduction of LDL or defective clearance of LDL particles Segregation analysis of LDL subclasses in these two types of families was performed to search for a single major genetic locus and to simultaneously test for the influence of polygenes and environmental effects The relationships between the LDL subclass phenotype characterized by a predominance of small dense LDL and overproduction of apoprotein B and LDL clearance defects were investigated in family members A determination was made as to whether an age-of-onset effect existed for the expression of LDL subclass phenotypes Genetic-environmental interactions were also studied
Low density lipoprotein cholesterol has been convincingly established as a major coronary heart disease risk factor by many epidemiologic studies clinical trials and experimental studies A strong inverse association exists between high density lipoprotein cholesterol and coronary heart disease However the status of very low density lipoprotein VLDL cholesterol and plasma triglyceride levels as independent risk factors for cardiovascular disease is less clear Case control studies have shown a positive association between coronary heart disease and plasma levels of apoprotein B the major protein on LDL particles and an inverse relationship with apoprotein AI the primary protein constituent of HDL particles In fact it has been proposed that plasma levels of the apoproteins may be stronger risk factors than lipid levels Thus understanding the mechanisms underlying variations in both lipoprotein and apoprotein levels among individuals is essential to elucidating the etiology of coronary heart disease in the general population
Cardiovascular disease is also known to cluster in families and this may be related to the clustering of lipid and lipoprotein levels among family members A review suggested that the familial aggregation of heart disease may be primarily a reflection of the familial aggregation of known risk factors including cholesterol levels The work of Goldstein and Brown on familial hypercholesterolemia demonstrated that genetic control of lipoprotein metabolism can play a causative role in the development of atherosclerosis However familial hypercholesterolemia is a relatively rare disorder the prevalence of heterozygotes is estimated to be 1 in 500 homozygotes 1 in a million In 1987 little was understood about more common genetic contributions to lipid and lipoprotein abnormalities leading to the familial aggregation of coronary heart disease
DESIGN NARRATIVE
The design was that of a cross-sectional family study The recruitment and screening of probands were conducted over a four-year period at the University of Texas at Dallas under separate funding The recruitment and screening of first-degree relatives were carried out at Berkeley Blood samples were obtained from relatives for LDL subclass analysis and for lipid and apoprotein determination An interview was conducted to obtain demographic information and information on behavioral and environmental risk factors such as smoking exercise and diet The data were used to determine whether LDL subclasses were genetically controlled in families with hypercholesterolemia due to overproduction of LDL or defective clearance of LDL particles Segregation analysis of LDL subclasses in these two types of families was performed to search for a single major genetic locus and to simultaneously test for the influence of polygenes and environmental effects The relationships between the LDL subclass phenotype characterized by a predominance of small dense LDL and overproduction of apoprotein B and LDL clearance defects were investigated in family members A determination was made as to whether an age-of-onset effect existed for the expression of LDL subclass phenotypes Genetic-environmental interactions were also studied
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R29HL038760 | NIH | None | httpsreporternihgovquickSearchR29HL038760 |