女性体内镉、铅、汞与对氧磷酶1活性的关联
Association of cadmium, lead and mercury with paraoxonase 1 activity in women.
作者信息
Pollack Anna Z, Sjaarda Lindsey, Ahrens Katherine A, Mumford Sunni L, Browne Richard W, Wactawski-Wende Jean, Schisterman Enrique F
机构信息
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, Maryland, United States of America; Department of Global and Community Health, School of Health and Human Services, George Mason University, Fairfax, Virginia, United States of America.
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
出版信息
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.
背景
对氧磷酶1（PON1）是一种抗氧化酶，其多态性与癌症风险相关，其活性可能与金属暴露有关。
目的
评估健康绝经前女性中PON1活性与镉、铅和汞水平的关系。
方法
对纽约州北部的女性进行了≥两个月经周期的随访。重复测量线性混合模型分别估计了镉、铅和汞水平（按三分位数：T1、T2、T3）与PON1芳基酯酶（PON1A）和PON1对氧磷酶（PON1P）活性之间的关联。分析按PON1 Q192R表型分层和未分层进行。
结果
血镉、铅和汞的中位数浓度分别为0.30μg/L、0.87μg/dL和1.15μg/L。在未分层分析中，镉和汞与PON1A活性降低有关（T2与T1相比；而非T3与T1相比），但金属与PON1P无关。表型分布在QQ（n = 99）、QR（n = 117）和RR（n = 34）之间。比较T2与T1时，镉与QR和RR表型的PON1A活性降低有关（-14.4%，95%置信区间[CI][-20.1，-8.4]和-27.9%[-39.5，-14.0]）。铅与PON1A降低有关（RR表型，T3与T1相比-18.9%[-32.5，-2.5]；T2与T1相比-19.6%[-32.4，-4.4]）。比较T2与T1时，镉与RR（-34.9%[-51.5，-12.5]）和QR表型（-9.5%[-18.1，0.0]）的PON1P降低有关，但比较T3与T1时无关。镉与PON1P水平升高有关（QQ表型，T3与T1相比24.5%[7.0，44.9]），汞与PON1A水平升高有关（QQ表型，T3与T1相比6.2%[0.2，12.6]）。汞与PON1P降低有关（RR表型，T2与T1相比-22.8[-37.8，-4.1]）。
结论
血液中的金属与PON1活性有关，且这些影响因表型而异。然而，不存在线性剂量反应关系，这些发现有待重复验证。
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