title: Associations between PON1 enzyme activities in human ovarian follicular fluid and serum specimens.
abstract: The importance of high-density lipoprotein (HDL) particle components to reproduction is increasingly recognized, including the constituent paraoxonase 1 (PON1). However, the reliability characteristics of PON1 enzymes in ovarian follicular fluid (FF) as biomarkers for clinical and epidemiologic studies have not been described. Therefore, we characterized PON1 enzymes in FF and serum and assessed the impact of the PON1 Q192R polymorphism on associations between enzyme activities in two compartments. We also evaluated associations between HDL particle size and enzyme activities. We collected FF and serum from 171 women undergoing in vitro fertilization. PON1 activities were measured as paraoxonase and arylesterase activities, and HDL particle size was determined by 1H NMR spectrometry. Reliability indices for PON1 activities were characterized and we evaluated HDL particle sizes as predictors of PON1 enzyme activities. We found that PON1 enzyme activities were correlated between compartments, but higher in serum than in FF. For FF, the index of individuality (II) was low and the coefficient of variation (CV%) was high for paraoxonase activity overall (0.12 and 11.51%, respectively). However, IIs increased (0.33-1.30) and CV%s decreased (5.58%-8.52%) when stratified by PON1 Q192R phenotype. The intraclass correlation coefficient (ICC) for FF paraoxonase activity was high overall (0.89) but decreased when stratified by PON1 Q192R phenotype (0.43-0.75). We found similar, although more modest, patterns for FF arylesterase activity. For enzyme activities in serum, ICCs were close to 1.00 across all phenotypes. Additionally, different HDL particle sizes predicted PON1 enzyme activities according to PON1 Q192R phenotype. Overall, stratification by PON1 Q192R phenotype improved the reliability characteristics of FF PON1 enzymes as biomarkers for use in clinical investigations but diminished usefulness for epidemiologic studies. Thus, we recommend stratification by PON1 Q192R phenotype for clinical but not epidemiologic investigations, when employing FF PON1 enzyme activity biomarkers.
authors.affiliation: Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, New York, United States of America.
authors.forename: Keewan
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Environmental Health Sciences, University at Albany, State University of New York, Rensselaer, New York, United States of America.|Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, New York, United States of America.
authors.forename: Michael S
authors.identifier: http://orcid.org/0000-0002-0028-5494
authors.initials: MS
authors.lastname: Bloom
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California at San Francisco, San Francisco, California, United States of America.
authors.forename: Victor Y
authors.initials: VY
authors.lastname: Fujimoto
authors.affiliation: Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, State University of New York, Buffalo, New York, United States of America.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Browne
mesh_terms: D000328:Adult; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D008075:Lipoproteins, HDL; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human