Epidemiology of Genetic Factors in Lipid Metabolism

NCT ID: NCT00005214

Last Updated: 2021-10-01

Basic Information

• Recruitment Status: COMPLETED
• Study Classification: OBSERVATIONAL
• Study Start Date: 1988-04-30
• Study Completion Date: 1993-03-31

Brief Summary

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

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.

Conditions

Cardiovascular Diseases; Heart Diseases; Atherosclerosis

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: CROSS_SECTIONAL

Eligibility Criteria

Inclusion Criteria

No eligibility criteria

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Eric Boerwinkle

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

References

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Reference Type: BACKGROUND

PMID: 8696957 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2911570 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2567503 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2816943 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2307462 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2139920 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1693506 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2383930 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2395672 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2216752 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1977654 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2263508 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1356882 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1427859 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1386087 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1733865 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1645755 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1746549 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1936612 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 1867194 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 8541836 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 8536954 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 7600116 (View on PubMed)

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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

PMID: 8304350 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 8353920 (View on PubMed)

Other Identifiers

R29HL040613

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1093

Identifier Type: -

Identifier Source: org_study_id