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Measurement of serum PON-3 concentration: method evaluation, reference values, and influence of genotypes in a population-based study.

ABSTRACT: Experimental studies showed that paraoxonase-3 (PON3) retards lipoprotein oxidation. Our objective was to describe a new assay to measure serum PON3 concentrations and report their reference values in a population-based study. The influence of PON3 promoter polymorphisms and their relationships with PON1 and lipid profile were also studied. We generated an anti-PON3 antibody by inoculating rabbits with a synthetic peptide specific to mature PON3. This antibody was used to develop an ELISA. The average regression line of standard plots (n = 8) was y = 0.9587 (0.3392) log(10)x + 1.9466 (0.0861) [r(2) = 0.924 (0.0131); P < 0.001]. There was no cross reaction with PON1. Detection limit was 0.24 mg/l. Imprecision was ? 13.2%. Reference interval (n = 356) was 1.00-2.47 mg/l. PON3 was observed in HDL particles containing apolipoprotein (apo)A-I and PON1, but not apoA-II or apoE. Serum PON3 concentrations showed a moderate influence (about 10% variation) by PON3 promoter polymorphisms. Our study describes for the first time a method to measure serum PON3 concentrations. This method offers new opportunities in the investigation of the properties and role of PON3 in cardiovascular disease, with possible implications in clinical practice.

SUBMITTER: Aragones G

PROVIDER: S-EPMC3073463 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Measurement of serum PON-3 concentration: method evaluation, reference values, and influence of genotypes in a population-based study.

Aragonès Gerard G Guardiola Marta M Barreda María M Marsillach Judit J Beltrán-Debón Raúl R Rull Anna A Mackness Bharti B Mackness Michael M Joven Jorge J Simó Josep M JM Camps Jordi J

Journal of lipid research 20110217 5

Experimental studies showed that paraoxonase-3 (PON3) retards lipoprotein oxidation. Our objective was to describe a new assay to measure serum PON3 concentrations and report their reference values in a population-based study. The influence of PON3 promoter polymorphisms and their relationships with PON1 and lipid profile were also studied. We generated an anti-PON3 antibody by inoculating rabbits with a synthetic peptide specific to mature PON3. This antibody was used to develop an ELISA. The a ...[more]

PMID: 21335322

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Project description:BackgroundTherapeutic drug monitoring for voriconazole is recommended for its optimum pharmacotherapy. Although the feedback of the measurement result of serum voriconazole concentration by outsourcing needs a certain time (days within a 1 week), there was no medical equipment for the measurement available in clinical practice. Recently, a medical equipment based on high performance liquid chromatography, named LM1010, has been developed and authorized for clinical use. In this study, to validate the clinical performance of LM1010, we compared the measured serum voriconazole concentrations by LM1010 with those by outsourcing measurement using liquid chromatography-tandem mass spectrometry.MethodsWe conducted the observational study approved by the institutional review board of Kumamoto University Hospital (No. 1786). Residual serum samples harvested for therapeutic drug monitoring were separated. Measured concentrations by LM1010 by the standard filter method (needs serum volume of > 400 μL) or the dilute method (needs serum volume of 150 μL) were compared with those by outsourcing, respectively. Acceptable measurement error range of 0.72-1.33 was considered. There were 69 serum samples, where the 35 or 34 samples were employed for evaluation of the standard filter method or the dilute method, respectively.ResultsThe measured concentration using the standard filter method/outsourcing was 2.22/2.10 μg/mL as the median, 1.57-3.40/1.53-3.62 as the interquartile range, < 0.2-10.76/< 0.2-11.46 μg/mL as the range, while those using the dilute method/outsourcing was 2.36/2.29 μg/mL as the median, 1.08-2.94/1.03-3.06 as the interquartile range, 0.24-10.00/< 0.2-10.85 μg/mL as the range. The regression line for the standard filter method or the dilute method were y = 0.935x + 0.154 or y = 0.933x + 0.162, respectively. The standard filter method or the dilute method showed 11.4% samples (4/35, 95%CI 3.2-26.7%) or 8.8% samples (3/34, 95%CI 1.9-23.7%) out of the acceptable measurement error range, respectively.ConclusionMeasurement of serum voriconazole concentration by LM1010 can be acceptable in clinical TDM practice.

Dataset Information

Measurement of serum PON-3 concentration: method evaluation, reference values, and influence of genotypes in a population-based study.

Publications

Measurement of serum PON-3 concentration: method evaluation, reference values, and influence of genotypes in a population-based study.

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