A DNA polymorphism for LCAT is associated with altered LCAT activity and high density lipoprotein size distributions in baboons

David L. Rainwater, John Blangero, James E. Hixson, Shifra Birnbaum, Glen E. Mott, John L. VandeBerg

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

A polymorphic Pvu II site was mapped to intron 5 of LCAT, the gene encoding baboon lecithin:cholesterol acyltransferase (LCAT). In a study of 83 baboons, heterozygous baboons (Pv1/Pv2) had significantly higher LCAT enzyme activity levels than did baboons homozygous for the more common allele (Pv1/Pv1). LCAT genotype explained 6% of the total variation in LCAT enzyme activity. To test for allelic effects on cholesterol metabolism, we compared serum concentrations of high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I). We also compared distributions of cholesterol and apo A-I among three HDL size classes (HDL1, HDL2, and HDL3). All measurements were obtained for each baboon after long-term feeding of a basal diet low in cholesterol and fat and again after 7 weeks on an atherogenic diet. Heterozygous baboons had significantly lower serum levels of total cholesterol than did homozygotes. In addition, we detected significant effects of LCAT genotype on size distributions of HDL cholesterol and apo A-I on both diets but did not detect any genotype-by-diet interaction. Heterozygotes had increased amounts of cholesterol and apo A-I in HDL3 particles and lower amounts of cholesterol and apo A-I in the larger HDL size classes by comparison with homozygotes. Overall, the LCAT polymorphism explained a significant proportion of total variation in cholesterol (4-10%) and apo A-I (13%) distributions on both diets. Thus, the results indicate that the LCAT polymorphism is associated with significant differences in LCAT enzyme activity and with alterations in HDL compositions.

Original languageEnglish (US)
Pages (from-to)682-690
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume12
Issue number6
StatePublished - 1992
Externally publishedYes

Fingerprint

Phosphatidylcholine-Sterol O-Acyltransferase
Papio
HDL Lipoproteins
Apolipoprotein A-I
Cholesterol
DNA
Diet
Genotype
Homozygote
HDL Cholesterol
Enzymes
Atherogenic Diet
Heterozygote
Serum
Introns
Fats
Alleles

Keywords

  • Apolipoprotein A-I
  • Baboons
  • Cholesterol
  • Gradient gel electrophoresis
  • High density lipoprotein subclasses
  • Lecithin:cholesterol acyltransferase
  • Restriction fragment length polymorphisms

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Rainwater, D. L., Blangero, J., Hixson, J. E., Birnbaum, S., Mott, G. E., & VandeBerg, J. L. (1992). A DNA polymorphism for LCAT is associated with altered LCAT activity and high density lipoprotein size distributions in baboons. Arteriosclerosis, Thrombosis, and Vascular Biology, 12(6), 682-690.

A DNA polymorphism for LCAT is associated with altered LCAT activity and high density lipoprotein size distributions in baboons. / Rainwater, David L.; Blangero, John; Hixson, James E.; Birnbaum, Shifra; Mott, Glen E.; VandeBerg, John L.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 12, No. 6, 1992, p. 682-690.

Research output: Contribution to journalArticle

Rainwater, DL, Blangero, J, Hixson, JE, Birnbaum, S, Mott, GE & VandeBerg, JL 1992, 'A DNA polymorphism for LCAT is associated with altered LCAT activity and high density lipoprotein size distributions in baboons', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 12, no. 6, pp. 682-690.
Rainwater, David L. ; Blangero, John ; Hixson, James E. ; Birnbaum, Shifra ; Mott, Glen E. ; VandeBerg, John L. / A DNA polymorphism for LCAT is associated with altered LCAT activity and high density lipoprotein size distributions in baboons. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 1992 ; Vol. 12, No. 6. pp. 682-690.
@article{903d9c49e3344ae58bb6c59d572aaea0,
title = "A DNA polymorphism for LCAT is associated with altered LCAT activity and high density lipoprotein size distributions in baboons",
abstract = "A polymorphic Pvu II site was mapped to intron 5 of LCAT, the gene encoding baboon lecithin:cholesterol acyltransferase (LCAT). In a study of 83 baboons, heterozygous baboons (Pv1/Pv2) had significantly higher LCAT enzyme activity levels than did baboons homozygous for the more common allele (Pv1/Pv1). LCAT genotype explained 6{\%} of the total variation in LCAT enzyme activity. To test for allelic effects on cholesterol metabolism, we compared serum concentrations of high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I). We also compared distributions of cholesterol and apo A-I among three HDL size classes (HDL1, HDL2, and HDL3). All measurements were obtained for each baboon after long-term feeding of a basal diet low in cholesterol and fat and again after 7 weeks on an atherogenic diet. Heterozygous baboons had significantly lower serum levels of total cholesterol than did homozygotes. In addition, we detected significant effects of LCAT genotype on size distributions of HDL cholesterol and apo A-I on both diets but did not detect any genotype-by-diet interaction. Heterozygotes had increased amounts of cholesterol and apo A-I in HDL3 particles and lower amounts of cholesterol and apo A-I in the larger HDL size classes by comparison with homozygotes. Overall, the LCAT polymorphism explained a significant proportion of total variation in cholesterol (4-10{\%}) and apo A-I (13{\%}) distributions on both diets. Thus, the results indicate that the LCAT polymorphism is associated with significant differences in LCAT enzyme activity and with alterations in HDL compositions.",
keywords = "Apolipoprotein A-I, Baboons, Cholesterol, Gradient gel electrophoresis, High density lipoprotein subclasses, Lecithin:cholesterol acyltransferase, Restriction fragment length polymorphisms",
author = "Rainwater, {David L.} and John Blangero and Hixson, {James E.} and Shifra Birnbaum and Mott, {Glen E.} and VandeBerg, {John L.}",
year = "1992",
language = "English (US)",
volume = "12",
pages = "682--690",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - A DNA polymorphism for LCAT is associated with altered LCAT activity and high density lipoprotein size distributions in baboons

AU - Rainwater, David L.

AU - Blangero, John

AU - Hixson, James E.

AU - Birnbaum, Shifra

AU - Mott, Glen E.

AU - VandeBerg, John L.

PY - 1992

Y1 - 1992

N2 - A polymorphic Pvu II site was mapped to intron 5 of LCAT, the gene encoding baboon lecithin:cholesterol acyltransferase (LCAT). In a study of 83 baboons, heterozygous baboons (Pv1/Pv2) had significantly higher LCAT enzyme activity levels than did baboons homozygous for the more common allele (Pv1/Pv1). LCAT genotype explained 6% of the total variation in LCAT enzyme activity. To test for allelic effects on cholesterol metabolism, we compared serum concentrations of high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I). We also compared distributions of cholesterol and apo A-I among three HDL size classes (HDL1, HDL2, and HDL3). All measurements were obtained for each baboon after long-term feeding of a basal diet low in cholesterol and fat and again after 7 weeks on an atherogenic diet. Heterozygous baboons had significantly lower serum levels of total cholesterol than did homozygotes. In addition, we detected significant effects of LCAT genotype on size distributions of HDL cholesterol and apo A-I on both diets but did not detect any genotype-by-diet interaction. Heterozygotes had increased amounts of cholesterol and apo A-I in HDL3 particles and lower amounts of cholesterol and apo A-I in the larger HDL size classes by comparison with homozygotes. Overall, the LCAT polymorphism explained a significant proportion of total variation in cholesterol (4-10%) and apo A-I (13%) distributions on both diets. Thus, the results indicate that the LCAT polymorphism is associated with significant differences in LCAT enzyme activity and with alterations in HDL compositions.

AB - A polymorphic Pvu II site was mapped to intron 5 of LCAT, the gene encoding baboon lecithin:cholesterol acyltransferase (LCAT). In a study of 83 baboons, heterozygous baboons (Pv1/Pv2) had significantly higher LCAT enzyme activity levels than did baboons homozygous for the more common allele (Pv1/Pv1). LCAT genotype explained 6% of the total variation in LCAT enzyme activity. To test for allelic effects on cholesterol metabolism, we compared serum concentrations of high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I). We also compared distributions of cholesterol and apo A-I among three HDL size classes (HDL1, HDL2, and HDL3). All measurements were obtained for each baboon after long-term feeding of a basal diet low in cholesterol and fat and again after 7 weeks on an atherogenic diet. Heterozygous baboons had significantly lower serum levels of total cholesterol than did homozygotes. In addition, we detected significant effects of LCAT genotype on size distributions of HDL cholesterol and apo A-I on both diets but did not detect any genotype-by-diet interaction. Heterozygotes had increased amounts of cholesterol and apo A-I in HDL3 particles and lower amounts of cholesterol and apo A-I in the larger HDL size classes by comparison with homozygotes. Overall, the LCAT polymorphism explained a significant proportion of total variation in cholesterol (4-10%) and apo A-I (13%) distributions on both diets. Thus, the results indicate that the LCAT polymorphism is associated with significant differences in LCAT enzyme activity and with alterations in HDL compositions.

KW - Apolipoprotein A-I

KW - Baboons

KW - Cholesterol

KW - Gradient gel electrophoresis

KW - High density lipoprotein subclasses

KW - Lecithin:cholesterol acyltransferase

KW - Restriction fragment length polymorphisms

UR - http://www.scopus.com/inward/record.url?scp=0026656638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026656638&partnerID=8YFLogxK

M3 - Article

C2 - 1350465

AN - SCOPUS:0026656638

VL - 12

SP - 682

EP - 690

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 6

ER -