Ignite Creation Date:
2024-05-05 @ 11:08 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005335
Status:
COMPLETED
Last Update Posted:
2016-05-13
First Post:
2000-05-25
Brief Title:
Genetic Epidemiology of Lipoprotein-Lipid Levels
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Heart Lung and Blood Institute NHLBI
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2004-07
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 determine the contribution of polymorphic variation in candidate genes involved in lipid metabolism in determining quantitative lipoprotein-lipid levels and cardiovascular risk factors in Anglo and Hispanic populations of the San Luis Valley in southern Colorado The candidate genes included those for A-IV B D E H APOa LDL receptor hepatic lipase lipoprotein lipase lethicin cholesterol acyletransferase LCAT and cholesteryl ester transfer protein
Detailed Description:
DESIGN NARRATIVE
Beginning in 1991 genetic variations in the gene products of A-IV E H and APOa were determined by isoelectric focusing and SDSimmunoblotting gene variations at the APOB D LDL receptor hepatic lipase lipoprotein lipase and cholesteryl ester transfer protein were assayed by polymerase chain reaction protocols and by using cloned cDNA probes for restriction fragment length polymorphism RFLP analyses Direct haplotype analyses of individuals employed a strategy using RFLP analysis combined with the use of allele specific oligonucleotides Quantitative levels of apolipoprotein B E H and APO a were determined by immunological techniques These data and prior data on levels of triglycerides total cholesterol HDL- LDL- and HDL subfraction cholesterol were used in the quantitative genetic analysis Estimates of the effect of alleles at each of the genetic loci on the quantitative apolipoprotein and lipoprotein levels employed the measured genotype approach The effects of multisite haplotypes for RFLPs at various loci were estimated using the same methods For common alleles in each system estimates were made of the interaction of alleles at independent genetic loci in determining quantitative variables Dietary information from the San Luis Valley population was used to estimate cholesterol intake identified Allelic effects were estimated in these groups to gain insight into the effect of dietary cholesterol intake of the estimated allelic effects
The study was renewed in fiscal year 1996 to determine the contribution of polymorphic variation in nine candidate genes involved in lipid metabolism APOa APOD hepatic lipase HL cholesteryl ester transfer protein CETP LDL receptor related protein LRP 3- hydroxy-3 methyl glutryl-coenzyme A HMG COA VLDL-receptor Lecithin cholesterol acyletransferase LCAT and paraoxonase PON in determining quantitative lipoprotein-lipid levels in Hispanics and non-Hispanic Whites of the San Luis Valley Colorado The study also determined the molecular basis of the functional mutation in the lipoprotein lipase LPL gene which is associated with plasma triglyceride and HDL cholesterol variations The objectives were achieved by fulfilling the following specific aims 1 by PCR DNA sequencing and SSCP analyses all coding exons and putative regulatory elements in the LPL gene of individuals who were homozygous for the HindIII restriction site to detect nucleotide changes in the coding region which affected directly triglycerides and HDL-cholesterol levels werescreened in vitro mutagenesis and expression studies were conducted to confirm which of the putative functional mutations was the actual functional mutation 2 genetic variations in genes coding for CETP HL LRP APOD HMG COA VLDL-receptor LCAT and PON were identified by PCR or standard Southern blotting techniques and the impact of individual polymorphisms and the joint impact of polymorphisms at different loci genotype-genotype interaction in determining quantitative lipoprotein-lipid levels in Hispanics and non-Hispanic whites were estimated and 3 the distribution of APOa kringle 4 and pentanucleotide polymorphisms were determined by SDS-agarose gel electrophoresis and PCR respectively and LPa levels were quantified by enzyme-linked immunosorbent assay and the correlation between APOa polymorphisms and LPa levels were investigated
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
Beginning in 1991 genetic variations in the gene products of A-IV E H and APOa were determined by isoelectric focusing and SDSimmunoblotting gene variations at the APOB D LDL receptor hepatic lipase lipoprotein lipase and cholesteryl ester transfer protein were assayed by polymerase chain reaction protocols and by using cloned cDNA probes for restriction fragment length polymorphism RFLP analyses Direct haplotype analyses of individuals employed a strategy using RFLP analysis combined with the use of allele specific oligonucleotides Quantitative levels of apolipoprotein B E H and APO a were determined by immunological techniques These data and prior data on levels of triglycerides total cholesterol HDL- LDL- and HDL subfraction cholesterol were used in the quantitative genetic analysis Estimates of the effect of alleles at each of the genetic loci on the quantitative apolipoprotein and lipoprotein levels employed the measured genotype approach The effects of multisite haplotypes for RFLPs at various loci were estimated using the same methods For common alleles in each system estimates were made of the interaction of alleles at independent genetic loci in determining quantitative variables Dietary information from the San Luis Valley population was used to estimate cholesterol intake identified Allelic effects were estimated in these groups to gain insight into the effect of dietary cholesterol intake of the estimated allelic effects
The study was renewed in fiscal year 1996 to determine the contribution of polymorphic variation in nine candidate genes involved in lipid metabolism APOa APOD hepatic lipase HL cholesteryl ester transfer protein CETP LDL receptor related protein LRP 3- hydroxy-3 methyl glutryl-coenzyme A HMG COA VLDL-receptor Lecithin cholesterol acyletransferase LCAT and paraoxonase PON in determining quantitative lipoprotein-lipid levels in Hispanics and non-Hispanic Whites of the San Luis Valley Colorado The study also determined the molecular basis of the functional mutation in the lipoprotein lipase LPL gene which is associated with plasma triglyceride and HDL cholesterol variations The objectives were achieved by fulfilling the following specific aims 1 by PCR DNA sequencing and SSCP analyses all coding exons and putative regulatory elements in the LPL gene of individuals who were homozygous for the HindIII restriction site to detect nucleotide changes in the coding region which affected directly triglycerides and HDL-cholesterol levels werescreened in vitro mutagenesis and expression studies were conducted to confirm which of the putative functional mutations was the actual functional mutation 2 genetic variations in genes coding for CETP HL LRP APOD HMG COA VLDL-receptor LCAT and PON were identified by PCR or standard Southern blotting techniques and the impact of individual polymorphisms and the joint impact of polymorphisms at different loci genotype-genotype interaction in determining quantitative lipoprotein-lipid levels in Hispanics and non-Hispanic whites were estimated and 3 the distribution of APOa kringle 4 and pentanucleotide polymorphisms were determined by SDS-agarose gel electrophoresis and PCR respectively and LPa levels were quantified by enzyme-linked immunosorbent assay and the correlation between APOa polymorphisms and LPa levels were investigated
The study completion date listed in this record was obtained from the End Date entered in the Protocol Registration and Results System PRS record
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 |
|---|---|---|---|
| R01HL044672 | NIH | None | httpsreporternihgovquickSearchR01HL044672 |