Association of Cadmium, Lead and Mercury With Paraoxonase 1 Activity in Women

Document Type

Article

Publication Date

3-28-2014

Publication Title

PLoS One

Abstract

Background: The activity of paraoxonase 1 (PON1), an antioxidant enzyme whose polymorphisms have been associated with cancer risk, may be associated with metals exposure. Objective: To evaluate PON1 activity in relation to cadmium, lead, and mercury levels in healthy, premenopausal women. Methods: Women from upstate New York were followed for ≥ two menstrual cycles. Repeated measures linear mixed models estimated the association between cadmium, lead, and mercury levels (by tertile: T1, T2, T3) and PON1 arylesterase (PON1A) and PON1 paraoxonase (PON1P) activity, separately. Analyses were stratified by PON1 Q192R phenotype and un-stratified. Results: Median blood cadmium, lead, and mercury concentrations were 0.30 µg/L, 0.87 µg/dL, and 1.15 µg/L. In un-stratified analyses cadmium and mercury were associated with decreased PON1A activity (T2 vs. T1; not T3 vs. T1) but metals were not associated with PON1P. Phenotypes were distributed between QQ (n = 99), QR (n = 117), and RR (n = 34). Cadmium was associated with decreased PON1A activity for QR and RR phenotypes comparing T2 vs. T1 (-14.4% 95% confidence interval [CI] [-20.1, -8.4] and -27.9% [-39.5, -14.0],). Lead was associated with decreased PON1A (RR phenotype, T3 vs. T1 -18.9% [-32.5, -2.5]; T2 vs. T1 -19.6% [-32.4, -4.4]). Cadmium was associated with lower PON1P comparing T2 vs. T1 for the RR (-34.9% [-51.5, -12.5]) and QR phenotypes (-9.5% [-18.1, 0.0]) but not comparing T3 vs. T1. Cadmium was associated with increases in PON1P levels (QQ phenotype, T3 vs. T1 24.5% [7.0, 44.9]) and mercury was associated with increased PON1A levels (QQ phenotype, T3 vs. T1 6.2% [0.2, 12.6]). Mercury was associated with decreased PON1P (RR phenotype, T2 vs. T1 -22.8 [-37.8, -4.1]). Conclusion: Blood metals were associated with PON1 activity and these effects varied by phenotype. However, there was not a linear dose-response and these findings await replication.

Comments

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (Contract # HHSN275200403394C). Anna Z. Pollack was partially supported by the Long-Range Research Initiative grant of the American Chemistry Council to Dr. Schisterman, PI, and partially supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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