Determinants of variation in human serum paraoxonase activity

D. L. Rainwater, S. Rutherford, T. D. Dyer, E. D. Rainwater, S. A. Cole, J. L. VandeBerg, L. Almasy, J. Blangero, J. W. MacCluer, M. C. Mahaney

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Paraoxonase-1 (PON1) is associated with high-density lipoprotein (HDL) particles and is believed to contribute to antiatherogenic properties of HDLs. We assessed the determinants of PON1 activity variation using different substrates of the enzyme. PON1 activity in serum samples from 922 participants in the San Antonio Family Heart Study was assayed using a reliable microplate format with three substrates: paraoxon, phenyl acetate and the lactone dihydrocoumarin. There were major differences among results from the three substrates in degree of effect by various environmental and genetic factors, suggesting that knowledge of one substrate activity alone may not provide a complete sense of PON1 metabolism. Three significant demographic covariates (age, smoking status and contraceptive usage) together explained 1-6% of phenotypic variance, whereas four metabolic covariates representing lipoprotein metabolism (apoAII, apoAI, triglycerides and non-HDL cholesterol) explained 4-19%. Genes explained 65-92% of phenotypic variance and the dominant genetic effect was exerted by a locus mapping at or near the protein structural locus (PON1) on chromosome 7. Additional genes influencing PON1 activity were localized to chromosomes 3 and 14. Our study identified environmental and genetic determinants of PON1 activity that accounted for 88-97% of total phenotypic variance, suggesting that few, if any, major biological determinants are unrepresented in the models.

Original languageEnglish (US)
Pages (from-to)147-154
Number of pages8
JournalHeredity
Volume102
Issue number2
DOIs
StatePublished - Feb 24 2009

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Aryldialkylphosphatase
Serum
Contraception Behavior
Paraoxon
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 3
Chromosomes, Human, Pair 7
Lactones
HDL Lipoproteins
Genes
Lipoproteins
Triglycerides
Smoking
Demography
Enzymes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Rainwater, D. L., Rutherford, S., Dyer, T. D., Rainwater, E. D., Cole, S. A., VandeBerg, J. L., ... Mahaney, M. C. (2009). Determinants of variation in human serum paraoxonase activity. Heredity, 102(2), 147-154. https://doi.org/10.1038/hdy.2008.110
Rainwater, D. L. ; Rutherford, S. ; Dyer, T. D. ; Rainwater, E. D. ; Cole, S. A. ; VandeBerg, J. L. ; Almasy, L. ; Blangero, J. ; MacCluer, J. W. ; Mahaney, M. C. / Determinants of variation in human serum paraoxonase activity. In: Heredity. 2009 ; Vol. 102, No. 2. pp. 147-154.
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Rainwater, DL, Rutherford, S, Dyer, TD, Rainwater, ED, Cole, SA, VandeBerg, JL, Almasy, L, Blangero, J, MacCluer, JW & Mahaney, MC 2009, 'Determinants of variation in human serum paraoxonase activity', Heredity, vol. 102, no. 2, pp. 147-154. https://doi.org/10.1038/hdy.2008.110

Determinants of variation in human serum paraoxonase activity. / Rainwater, D. L.; Rutherford, S.; Dyer, T. D.; Rainwater, E. D.; Cole, S. A.; VandeBerg, J. L.; Almasy, L.; Blangero, J.; MacCluer, J. W.; Mahaney, M. C.

In: Heredity, Vol. 102, No. 2, 24.02.2009, p. 147-154.

Research output: Contribution to journalArticle

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Rainwater DL, Rutherford S, Dyer TD, Rainwater ED, Cole SA, VandeBerg JL et al. Determinants of variation in human serum paraoxonase activity. Heredity. 2009 Feb 24;102(2):147-154. https://doi.org/10.1038/hdy.2008.110