Association of cadmium, lead and mercury with paraoxonase 1 activity in women

PLoS One. 2014 Mar 28;9(3):e92152. doi: 10.1371/journal.pone.0092152. eCollection 2014.


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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aryldialkylphosphatase / metabolism*
  • Cadmium / blood*
  • Female
  • Humans
  • Lead / blood*
  • Mercury / blood*
  • New York
  • Phenotype
  • Premenopause / blood
  • Premenopause / metabolism


  • Cadmium
  • Lead
  • Aryldialkylphosphatase
  • PON1 protein, human
  • Mercury