Determinants of variation in serum paraoxonase enzyme activity in baboons

David L. Rainwater, Michael C. Mahaney, Xing Li Wang, Jeffrey Rogers, Laura A. Cox, John L. Vandeberg

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Paraoxonase (PON), an HDL-associated enzyme, is one of many circulating antioxidants thought to play a vital protective role. To better understand the determinants of quantitative variation in serum PON activity, we assayed PON in samples from 611 pedigreed baboons fed three diets. PON was measured enzymatically; the main determinant of variation was genetic and consisted of at least three components: two loci detected by linkage analyses and a residual polygenic component. Multipoint linkage analyses gave peak log of the odds (LOD) scores on the baboon homolog of human chromosome 7q21-22 (near PON1, the structural gene) of 9.1 on the low-cholesterol, high-fat diet and 4.1 on the high-cholesterol, high-fat diet (genome-wide P values were 1 × 10 -8 and 0.0018, respectively). Surprisingly, a second locus on the baboon homolog of human chromosome 12q13 gave a LOD score of 2.9 on the high-cholesterol, high-fat diet (genome-wide P value was 0.032). We identified several significant covariates, including age, sex, diet, and apolipoprotein A-I concentrations. We estimate that 53% of total trait variation in baboons is explained by genes and 17% by covariates, thus accounting for ∼70% of total variation in baboon PON. Although the generation of free radicals is influenced primarily by environmental factors, our findings suggest strong genetic regulation of one component in the antioxidant defense system that plays a major role in susceptibility to atherosclerosis.

Original languageEnglish (US)
Pages (from-to)1450-1456
Number of pages7
JournalJournal of Lipid Research
Volume46
Issue number7
DOIs
StatePublished - 2005
Externally publishedYes

Fingerprint

Aryldialkylphosphatase
Papio
Enzyme activity
Nutrition
High Fat Diet
Genes
Enzymes
Serum
Fats
Cholesterol
Human Chromosomes
Chromosomes
Antioxidants
Genome
Diet
Chromosomes, Human, Pair 22
Apolipoprotein A-I
Free Radicals
Atherosclerosis

Keywords

  • Genetic
  • Linkage analysis
  • PON1

ASJC Scopus subject areas

  • Endocrinology

Cite this

Rainwater, D. L., Mahaney, M. C., Wang, X. L., Rogers, J., Cox, L. A., & Vandeberg, J. L. (2005). Determinants of variation in serum paraoxonase enzyme activity in baboons. Journal of Lipid Research, 46(7), 1450-1456. https://doi.org/10.1194/jlr.M400473-JLR200

Determinants of variation in serum paraoxonase enzyme activity in baboons. / Rainwater, David L.; Mahaney, Michael C.; Wang, Xing Li; Rogers, Jeffrey; Cox, Laura A.; Vandeberg, John L.

In: Journal of Lipid Research, Vol. 46, No. 7, 2005, p. 1450-1456.

Research output: Contribution to journalArticle

Rainwater, DL, Mahaney, MC, Wang, XL, Rogers, J, Cox, LA & Vandeberg, JL 2005, 'Determinants of variation in serum paraoxonase enzyme activity in baboons', Journal of Lipid Research, vol. 46, no. 7, pp. 1450-1456. https://doi.org/10.1194/jlr.M400473-JLR200
Rainwater, David L. ; Mahaney, Michael C. ; Wang, Xing Li ; Rogers, Jeffrey ; Cox, Laura A. ; Vandeberg, John L. / Determinants of variation in serum paraoxonase enzyme activity in baboons. In: Journal of Lipid Research. 2005 ; Vol. 46, No. 7. pp. 1450-1456.
@article{e1c8b2708f194c068fce256563b5a8ff,
title = "Determinants of variation in serum paraoxonase enzyme activity in baboons",
abstract = "Paraoxonase (PON), an HDL-associated enzyme, is one of many circulating antioxidants thought to play a vital protective role. To better understand the determinants of quantitative variation in serum PON activity, we assayed PON in samples from 611 pedigreed baboons fed three diets. PON was measured enzymatically; the main determinant of variation was genetic and consisted of at least three components: two loci detected by linkage analyses and a residual polygenic component. Multipoint linkage analyses gave peak log of the odds (LOD) scores on the baboon homolog of human chromosome 7q21-22 (near PON1, the structural gene) of 9.1 on the low-cholesterol, high-fat diet and 4.1 on the high-cholesterol, high-fat diet (genome-wide P values were 1 × 10 -8 and 0.0018, respectively). Surprisingly, a second locus on the baboon homolog of human chromosome 12q13 gave a LOD score of 2.9 on the high-cholesterol, high-fat diet (genome-wide P value was 0.032). We identified several significant covariates, including age, sex, diet, and apolipoprotein A-I concentrations. We estimate that 53{\%} of total trait variation in baboons is explained by genes and 17{\%} by covariates, thus accounting for ∼70{\%} of total variation in baboon PON. Although the generation of free radicals is influenced primarily by environmental factors, our findings suggest strong genetic regulation of one component in the antioxidant defense system that plays a major role in susceptibility to atherosclerosis.",
keywords = "Genetic, Linkage analysis, PON1",
author = "Rainwater, {David L.} and Mahaney, {Michael C.} and Wang, {Xing Li} and Jeffrey Rogers and Cox, {Laura A.} and Vandeberg, {John L.}",
year = "2005",
doi = "10.1194/jlr.M400473-JLR200",
language = "English (US)",
volume = "46",
pages = "1450--1456",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "7",

}

TY - JOUR

T1 - Determinants of variation in serum paraoxonase enzyme activity in baboons

AU - Rainwater, David L.

AU - Mahaney, Michael C.

AU - Wang, Xing Li

AU - Rogers, Jeffrey

AU - Cox, Laura A.

AU - Vandeberg, John L.

PY - 2005

Y1 - 2005

N2 - Paraoxonase (PON), an HDL-associated enzyme, is one of many circulating antioxidants thought to play a vital protective role. To better understand the determinants of quantitative variation in serum PON activity, we assayed PON in samples from 611 pedigreed baboons fed three diets. PON was measured enzymatically; the main determinant of variation was genetic and consisted of at least three components: two loci detected by linkage analyses and a residual polygenic component. Multipoint linkage analyses gave peak log of the odds (LOD) scores on the baboon homolog of human chromosome 7q21-22 (near PON1, the structural gene) of 9.1 on the low-cholesterol, high-fat diet and 4.1 on the high-cholesterol, high-fat diet (genome-wide P values were 1 × 10 -8 and 0.0018, respectively). Surprisingly, a second locus on the baboon homolog of human chromosome 12q13 gave a LOD score of 2.9 on the high-cholesterol, high-fat diet (genome-wide P value was 0.032). We identified several significant covariates, including age, sex, diet, and apolipoprotein A-I concentrations. We estimate that 53% of total trait variation in baboons is explained by genes and 17% by covariates, thus accounting for ∼70% of total variation in baboon PON. Although the generation of free radicals is influenced primarily by environmental factors, our findings suggest strong genetic regulation of one component in the antioxidant defense system that plays a major role in susceptibility to atherosclerosis.

AB - Paraoxonase (PON), an HDL-associated enzyme, is one of many circulating antioxidants thought to play a vital protective role. To better understand the determinants of quantitative variation in serum PON activity, we assayed PON in samples from 611 pedigreed baboons fed three diets. PON was measured enzymatically; the main determinant of variation was genetic and consisted of at least three components: two loci detected by linkage analyses and a residual polygenic component. Multipoint linkage analyses gave peak log of the odds (LOD) scores on the baboon homolog of human chromosome 7q21-22 (near PON1, the structural gene) of 9.1 on the low-cholesterol, high-fat diet and 4.1 on the high-cholesterol, high-fat diet (genome-wide P values were 1 × 10 -8 and 0.0018, respectively). Surprisingly, a second locus on the baboon homolog of human chromosome 12q13 gave a LOD score of 2.9 on the high-cholesterol, high-fat diet (genome-wide P value was 0.032). We identified several significant covariates, including age, sex, diet, and apolipoprotein A-I concentrations. We estimate that 53% of total trait variation in baboons is explained by genes and 17% by covariates, thus accounting for ∼70% of total variation in baboon PON. Although the generation of free radicals is influenced primarily by environmental factors, our findings suggest strong genetic regulation of one component in the antioxidant defense system that plays a major role in susceptibility to atherosclerosis.

KW - Genetic

KW - Linkage analysis

KW - PON1

UR - http://www.scopus.com/inward/record.url?scp=24744440594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=24744440594&partnerID=8YFLogxK

U2 - 10.1194/jlr.M400473-JLR200

DO - 10.1194/jlr.M400473-JLR200

M3 - Article

VL - 46

SP - 1450

EP - 1456

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 7

ER -