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CompletedNCT00005214Updated Oct 1, 2021

Epidemiology of Genetic Factors in Lipid Metabolism

An observational study in Cardiovascular Diseases, Heart Diseases and Atherosclerosis, sponsored by The University of Texas Health Science Center, Houston. Completed. Open to participants aged 0 Years to 100 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-10-01.

Sponsored by The University of Texas Health Science Center, Houston · Observational

Study type
Observational
Model
Case-only
Time perspective
Cross-sectional
Ages
0 Years to 100 Years
Sex
All
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Study summary

To investigate the genetics and epidemiology of fasting and postprandial lipid, lipoprotein, and apolipoprotein levels.

Read the detailed description

BACKGROUND:

Altered plasma lipid, lipoprotein, and apolipoprotein levels are associated with the occurrence of coronary heart disease, non-insulin dependent diabetes, and gallbladder disease. Although there are many other environmental and biological correlates, clinical, epidemiological, and experimental lines of evidence indicate that lipid metabolism has a central role in the development of coronary heart disease. Evidence pointing to the association between measures of lipid metabolism and other chronic diseases is no less compelling. Non-insulin dependent diabetes mellitus exhibits both the diagnostic abnormal carbohydrate utilization, and altered lipid metabolism. The hypothesis that abnormal lipid metabolism may be causally involved in gallbladder disease is suggested by the presence of cholesterol saturated bile several years prior to the onset of clinically definable gallstones.

Biometrical genetic studies have established that a significant proportion of the fasting plasma lipid, lipoprotein, and apolipoprotein levels is attributable to genetic differences among individuals. Although these studies indicate that polygenetic variability is contributing, they do not yield information about specific candidate genes whose products are involved in the metabolism of the phenotype of interest. Recent advances in molecular biology enable one to measure genetic variability at candidate loci for several risk factors for the common chronic diseases. With this information the contribution of specific candidate genes to polygenetic and phenotypic variability can be estimated. Estimating the effects of specific candidate loci will facilitate the investigation of the interaction between genetic and environmental factors. This study focussed on restriction fragment length polymorphisms in and around the apolipoprotein B gene and on the apolipoprotein E protein polymorphism. The apolipoprotein B and apolipoprotein E genes were selected because of their central role in lipid metabolism and interaction with dietary factors.

DESIGN NARRATIVE:

Using data and blood samples from the 75 nuclear families of Nancy, a determination was made of the effects of apolipoprotein B and E genes on fasting levels of total cholesterol and triglycerides, LDL-cholesterol, HDL-cholesterol, HDL2-cholesterol, HDL3-cholesterol, apo A-I, apo-B, apo C-III, and apo-E. Genetic variability was directly assessed by DNA restriction site variability in the apolipoprotein B gene and by measuring the apolipoprotein E polymorphism. Data collected from these families permitted the partitioning of the effects of the apolipoprotein B and E genes from the overall polygenetic and phenotypic variance of the measured lipids, lipoproteins, and apolipoproteins.

Fasting and postprandial lipids, lipoproteins, and apolipoproteins were obtained from 100 Mexican-American women. A determination was made of the effects of apolipoprotein E and B genes, disease status, age, and their interactions on fasting and postprandial lipid metabolism.

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Conditions studied

  • Cardiovascular Diseases
  • Heart Diseases
  • Atherosclerosis
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In context

Cardiovascular Diseases

4,904 studies on the registry are indexed under Cardiovascular Diseases; 919 are open to participants now.

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Lead sponsor

The University of Texas Health Science Center, Houston is the lead sponsor of 880 studies on the registry; 209 are open to participants now.

Of its 170 completed or terminated interventional studies of FDA-regulated products, 140 (82%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
0 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Study population

Sample of 75 nuclear families from Nancy France. Sample of 100 unrelated Mexican-Americans from Laredo, Texas.

Eligibility criteria

No eligibility criteria

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Study design

Observational model
Case-only
Time perspective
Cross-sectional
Biospecimen retention
Samples with dna
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Study locations

No study locations are listed for this record.

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References and documents

Publications

  • Surguchov AP, Page GP, Smith L, Patsch W, Boerwinkle E. Polymorphic markers in apolipoprotein C-III gene flanking regions and hypertriglyceridemia. Arterioscler Thromb Vasc Biol. 1996 Aug;16(8):941-7. doi: 10.1161/01.atv.16.8.941. PubMed 8696957 ↗
  • Boerwinkle E, Xiong WJ, Fourest E, Chan L. Rapid typing of tandemly repeated hypervariable loci by the polymerase chain reaction: application to the apolipoprotein B 3' hypervariable region. Proc Natl Acad Sci U S A. 1989 Jan;86(1):212-6. doi: 10.1073/pnas.86.1.212. PubMed 2911570 ↗
  • Boerwinkle E, Chan L. A three codon insertion/deletion polymorphism in the signal peptide region of the human apolipoprotein B (APOB) gene directly typed by the polymerase chain reaction. Nucleic Acids Res. 1989 May 25;17(10):4003. doi: 10.1093/nar/17.10.4003. PubMed 2567503 ↗
  • Gueguen R, Visvikis S, Steinmetz J, Siest G, Boerwinkle E. An analysis of genotype effects and their interactions by using the apolipoprotein E polymorphism and longitudinal data. Am J Hum Genet. 1989 Nov;45(5):793-802. PubMed 2816943 ↗
  • Visvikis S, Chan L, Siest G, Drouin P, Boerwinkle E. An insertion deletion polymorphism in the signal peptide of the human apolipoprotein B gene. Hum Genet. 1990 Mar;84(4):373-5. doi: 10.1007/BF00196239. PubMed 2307462 ↗
  • Seed M, Hoppichler F, Reaveley D, McCarthy S, Thompson GR, Boerwinkle E, Utermann G. Relation of serum lipoprotein(a) concentration and apolipoprotein(a) phenotype to coronary heart disease in patients with familial hypercholesterolemia. N Engl J Med. 1990 May 24;322(21):1494-9. doi: 10.1056/NEJM199005243222104. PubMed 2139920 ↗
  • Boerwinkle E, Lee SS, Butler R, Schumaker VN, Chan L. Rapid typing of apolipoprotein B DNA polymorphisms by DNA amplification. Association between Ag epitopes of human apolipoprotein B-100, a signal peptide insertion/deletion polymorphism, and a 3'flanking DNA variable number of tandem repeats polymorphism of the apolipoprotein B gene. Atherosclerosis. 1990 Apr;81(3):225-32. doi: 10.1016/0021-9150(90)90070-y. PubMed 1693506 ↗
  • Visvikis S, Steinmetz J, Boerwinkle E, Gueguen R, Galteau MM, Siest G. Frequency and effects of the apolipoprotein A-IV polymorphism. Clin Genet. 1990 Jun;37(6):435-41. doi: 10.1111/j.1399-0004.1990.tb03527.x. PubMed 2383930 ↗
  • Boerwinkle E, Visvikis S, Chan L. Two polymorphisms for amino acid substitutions in the APOA4 gene. Nucleic Acids Res. 1990 Aug 25;18(16):4966. doi: 10.1093/nar/18.16.4966. No abstract available. PubMed 2395672 ↗
  • de Temmerman P, Visvikis S, Boerwinkle E, Siest G. Study of the sequence tagged site (STS) in the beginning of human apo A4 gene region. Nucleic Acids Res. 1990 Sep 25;18(18):5576. doi: 10.1093/nar/18.18.5576. PubMed 2216752 ↗
  • Xu CF, Boerwinkle E, Tikkanen MJ, Huttunen JK, Humphries SE, Talmud PJ. Genetic variation at the apolipoprotein gene loci contribute to response of plasma lipids to dietary change. Genet Epidemiol. 1990;7(4):261-75. doi: 10.1002/gepi.1370070405. PubMed 1977654 ↗
  • Boerwinkle E, Hanis CL, Chan L. A unique length polymorphism in the signal peptide region of the apolipoprotein B gene in Mexican-Americans. Nucleic Acids Res. 1990 Dec 11;18(23):7193. doi: 10.1093/nar/18.23.7193. PubMed 2263508 ↗
  • Talmud PJ, Boerwinkle E, Xu CF, Tikkanen MJ, Pietinen P, Huttunen JK, Humphries S. Dietary intake and gene variation influence the response of plasma lipids to dietary intervention. Genet Epidemiol. 1992;9(4):249-60. doi: 10.1002/gepi.1370090404. PubMed 1356882 ↗
  • Shriver MD, Siest G, Boerwinkle E. Length and sequence variation in the apolipoprotein B intron 20 Alu repeat. Genomics. 1992 Oct;14(2):449-54. doi: 10.1016/s0888-7543(05)80240-x. PubMed 1427859 ↗
  • Boerwinkle E, Leffert CC, Lin J, Lackner C, Chiesa G, Hobbs HH. Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations. J Clin Invest. 1992 Jul;90(1):52-60. doi: 10.1172/JCI115855. PubMed 1386087 ↗
  • Fornage M, Chan L, Siest G, Boerwinkle E. Allele frequency distribution of the (TG)n(AG)m microsatellite in the apolipoprotein C-II gene. Genomics. 1992 Jan;12(1):63-8. doi: 10.1016/0888-7543(92)90407-j. PubMed 1733865 ↗
  • Lackner C, Boerwinkle E, Leffert CC, Rahmig T, Hobbs HH. Molecular basis of apolipoprotein (a) isoform size heterogeneity as revealed by pulsed-field gel electrophoresis. J Clin Invest. 1991 Jun;87(6):2153-61. doi: 10.1172/JCI115248. Erratum In: J Clin Invest 1991 Aug;88(2):723. PubMed 1645755 ↗
  • Boerwinkle E, Brown SA, Rohrbach K, Gotto AM Jr, Patsch W. Role of apolipoprotein E and B gene variation in determining response of lipid, lipoprotein, and apolipoprotein levels to increased dietary cholesterol. Am J Hum Genet. 1991 Dec;49(6):1145-54. PubMed 1746549 ↗
  • Boerwinkle E, Chen SH, Visvikis S, Hanis CL, Siest G, Chan L. Signal peptide-length variation in human apolipoprotein B gene. Molecular characteristics and association with plasma glucose levels. Diabetes. 1991 Nov;40(11):1539-44. doi: 10.2337/diab.40.11.1539. PubMed 1936612 ↗
  • Hallman DM, Boerwinkle E, Saha N, Sandholzer C, Menzel HJ, Csazar A, Utermann G. The apolipoprotein E polymorphism: a comparison of allele frequencies and effects in nine populations. Am J Hum Genet. 1991 Aug;49(2):338-49. PubMed 1867194 ↗
  • Mancini FP, Mooser V, Guerra R, Hobbs HH. Sequence microheterogeneity in apolipoprotein(a) gene repeats and the relationship to plasma Lp(a) levels. Hum Mol Genet. 1995 Sep;4(9):1535-42. doi: 10.1093/hmg/4.9.1535. PubMed 8541836 ↗
  • Carrejo MH, Sharrett R, Patsch W, Boerwinkle E. No association of apolipoprotein A-IV codon 347 and 360 variation with atherosclerosis and lipid transport in a sample of mixed hyperlipidemics. Genet Epidemiol. 1995;12(4):371-80. doi: 10.1002/gepi.1370120405. PubMed 8536954 ↗
  • Moliterno DJ, Jokinen EV, Miserez AR, Lange RA, Willard JE, Boerwinkle E, Hillis LD, Hobbs HH. No association between plasma lipoprotein(a) concentrations and the presence or absence of coronary atherosclerosis in African-Americans. Arterioscler Thromb Vasc Biol. 1995 Jul;15(7):850-5. doi: 10.1161/01.atv.15.7.850. PubMed 7600116 ↗
  • de Andrade M, Thandi I, Brown S, Gotto A Jr, Patsch W, Boerwinkle E. Relationship of the apolipoprotein E polymorphism with carotid artery atherosclerosis. Am J Hum Genet. 1995 Jun;56(6):1379-90. PubMed 7762561 ↗
  • Hallman DM, Visvikis S, Steinmetz J, Boerwinkle E. The effect of variation in the apolipoprotein B gene on plasmid lipid and apolipoprotein B levels. I. A likelihood-based approach to cladistic analysis. Ann Hum Genet. 1994 Jan;58(1):35-64. doi: 10.1111/j.1469-1809.1994.tb00724.x. PubMed 8031014 ↗
  • Boerwinkle E, Brown S, Sharrett AR, Heiss G, Patsch W. Apolipoprotein E polymorphism influences postprandial retinyl palmitate but not triglyceride concentrations. Am J Hum Genet. 1994 Feb;54(2):341-60. PubMed 8304350 ↗
  • Moliterno DJ, Lange RA, Meidell RS, Willard JE, Leffert CC, Gerard RD, Boerwinkle E, Hobbs HH, Hillis LD. Relation of plasma lipoprotein(a) to infarct artery patency in survivors of myocardial infarction. Circulation. 1993 Sep;88(3):935-40. doi: 10.1161/01.cir.88.3.935. PubMed 8353920 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 1, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00005214
Lead sponsor
The University of Texas Health Science Center, Houston
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Responsible party
Eric Boerwinkle (Professor, The University of Texas Health Science Center, Houston) — Principal investigator
First posted
May 26, 2000
Start date
Apr 1988
Completion
Mar 1993
Last update
Oct 1, 2021

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.

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