Methods for measuring serum activity levels of the 192 Q and R isoenzymes of paraoxonase 1 in QR heterozygous individuals

John F. Teiber, Gerald L. Kramer, Robert W. Haley

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

BACKGROUND: Paraoxonase 1 (PON1), an esterase that hydrolyzes toxic organophosphates and has antioxidative and antiatherogenic properties, contains a common polymorphism at position 192: glutamine (Q) or arginine (R). TheQand R isoenzymes exhibit different physical and protective properties. We describe 2 methods for quantifying their serum activity levels. METHODS: We measured serum hydrolytic activity with paraoxon [paraoxonase (PXN) activity], phenylacetate [arylesterase (AE) activity], and diazoxon [diazoxonase (DZN) activity] with standard automated assays.WedeterminedPON1Q192Rgenotypes withPCRand Q192R phenotypes using the PXN/AE and PXN/DZN ratios. Interpolation equations were empirically derived to predict the percentage of total PON1 hydrolytic activity due to theQ isoenzyme (%Q) from the PXN/AE and PXN/DZN ratios; %R is 100%Q. We estimatedQand R isoenzyme activity levels in sera from 2095 veterans by multiplying AE activity, a measure of total PON1 hydrolytic activity, by%Qand %R. RESULTS: In all 2095 samples, the PXN/AE and PXN/ DZN ratios predicted Q192R phenotypes with nearly identical accuracy (Κ=0.997). In the 925QRheterozygotes, the 2 interpolation methods predicted Q and R isoenzyme activity levels with excellent agreement (intraclass correlation 0.94). After excluding a few genotype/phenotype-discordant samples, the percentage of total PON1 activity due to the Q isoenzyme ranged from 22% to 70%. CONCLUSIONS: These new interpolation methods allow accurate estimation of PON1 192 Q and R isoenzyme activity levels, increasing specificity and power for studying susceptibility to disease.

Original languageEnglish (US)
Pages (from-to)1251-1259
Number of pages9
JournalClinical Chemistry
Volume59
Issue number8
DOIs
StatePublished - Aug 2013

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Aryldialkylphosphatase
Isoenzymes
Serum
Interpolation
Phenotype
Paraoxon
Organophosphates
Poisons
Disease Susceptibility
Veterans
Esterases
Glutamine
Polymorphism
Arginine
Assays

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Methods for measuring serum activity levels of the 192 Q and R isoenzymes of paraoxonase 1 in QR heterozygous individuals. / Teiber, John F.; Kramer, Gerald L.; Haley, Robert W.

In: Clinical Chemistry, Vol. 59, No. 8, 08.2013, p. 1251-1259.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND: Paraoxonase 1 (PON1), an esterase that hydrolyzes toxic organophosphates and has antioxidative and antiatherogenic properties, contains a common polymorphism at position 192: glutamine (Q) or arginine (R). TheQand R isoenzymes exhibit different physical and protective properties. We describe 2 methods for quantifying their serum activity levels. METHODS: We measured serum hydrolytic activity with paraoxon [paraoxonase (PXN) activity], phenylacetate [arylesterase (AE) activity], and diazoxon [diazoxonase (DZN) activity] with standard automated assays.WedeterminedPON1Q192Rgenotypes withPCRand Q192R phenotypes using the PXN/AE and PXN/DZN ratios. Interpolation equations were empirically derived to predict the percentage of total PON1 hydrolytic activity due to theQ isoenzyme ({\%}Q) from the PXN/AE and PXN/DZN ratios; {\%}R is 100{\%}Q. We estimatedQand R isoenzyme activity levels in sera from 2095 veterans by multiplying AE activity, a measure of total PON1 hydrolytic activity, by{\%}Qand {\%}R. RESULTS: In all 2095 samples, the PXN/AE and PXN/ DZN ratios predicted Q192R phenotypes with nearly identical accuracy (Κ=0.997). In the 925QRheterozygotes, the 2 interpolation methods predicted Q and R isoenzyme activity levels with excellent agreement (intraclass correlation 0.94). After excluding a few genotype/phenotype-discordant samples, the percentage of total PON1 activity due to the Q isoenzyme ranged from 22{\%} to 70{\%}. CONCLUSIONS: These new interpolation methods allow accurate estimation of PON1 192 Q and R isoenzyme activity levels, increasing specificity and power for studying susceptibility to disease.",
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N2 - BACKGROUND: Paraoxonase 1 (PON1), an esterase that hydrolyzes toxic organophosphates and has antioxidative and antiatherogenic properties, contains a common polymorphism at position 192: glutamine (Q) or arginine (R). TheQand R isoenzymes exhibit different physical and protective properties. We describe 2 methods for quantifying their serum activity levels. METHODS: We measured serum hydrolytic activity with paraoxon [paraoxonase (PXN) activity], phenylacetate [arylesterase (AE) activity], and diazoxon [diazoxonase (DZN) activity] with standard automated assays.WedeterminedPON1Q192Rgenotypes withPCRand Q192R phenotypes using the PXN/AE and PXN/DZN ratios. Interpolation equations were empirically derived to predict the percentage of total PON1 hydrolytic activity due to theQ isoenzyme (%Q) from the PXN/AE and PXN/DZN ratios; %R is 100%Q. We estimatedQand R isoenzyme activity levels in sera from 2095 veterans by multiplying AE activity, a measure of total PON1 hydrolytic activity, by%Qand %R. RESULTS: In all 2095 samples, the PXN/AE and PXN/ DZN ratios predicted Q192R phenotypes with nearly identical accuracy (Κ=0.997). In the 925QRheterozygotes, the 2 interpolation methods predicted Q and R isoenzyme activity levels with excellent agreement (intraclass correlation 0.94). After excluding a few genotype/phenotype-discordant samples, the percentage of total PON1 activity due to the Q isoenzyme ranged from 22% to 70%. CONCLUSIONS: These new interpolation methods allow accurate estimation of PON1 192 Q and R isoenzyme activity levels, increasing specificity and power for studying susceptibility to disease.

AB - BACKGROUND: Paraoxonase 1 (PON1), an esterase that hydrolyzes toxic organophosphates and has antioxidative and antiatherogenic properties, contains a common polymorphism at position 192: glutamine (Q) or arginine (R). TheQand R isoenzymes exhibit different physical and protective properties. We describe 2 methods for quantifying their serum activity levels. METHODS: We measured serum hydrolytic activity with paraoxon [paraoxonase (PXN) activity], phenylacetate [arylesterase (AE) activity], and diazoxon [diazoxonase (DZN) activity] with standard automated assays.WedeterminedPON1Q192Rgenotypes withPCRand Q192R phenotypes using the PXN/AE and PXN/DZN ratios. Interpolation equations were empirically derived to predict the percentage of total PON1 hydrolytic activity due to theQ isoenzyme (%Q) from the PXN/AE and PXN/DZN ratios; %R is 100%Q. We estimatedQand R isoenzyme activity levels in sera from 2095 veterans by multiplying AE activity, a measure of total PON1 hydrolytic activity, by%Qand %R. RESULTS: In all 2095 samples, the PXN/AE and PXN/ DZN ratios predicted Q192R phenotypes with nearly identical accuracy (Κ=0.997). In the 925QRheterozygotes, the 2 interpolation methods predicted Q and R isoenzyme activity levels with excellent agreement (intraclass correlation 0.94). After excluding a few genotype/phenotype-discordant samples, the percentage of total PON1 activity due to the Q isoenzyme ranged from 22% to 70%. CONCLUSIONS: These new interpolation methods allow accurate estimation of PON1 192 Q and R isoenzyme activity levels, increasing specificity and power for studying susceptibility to disease.

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